中国化学会生物物理化学专业委员会第四届全国生物物理化学会议 ·...

2016.6.14~2016.6.17

主办：中国化学会-生物物理化学专业委员会

承办：中国科学技术大学

协办：合肥微尺度物质科学国家实验室、中科院合肥大科学中心

中国化学会-生物物理化学专业委员会

第四届全国生物物理化学会议

第四届全国生物物理化学会议（NCBPC4）

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赞助单位：

尼康仪器（上海）有限公司

天津东方科捷科技有限公司

百灵威化学技术有限公司

北京东科泓生科技有限公司

上海复亨光学股份有限公司

上海艮泰信息技术有限公司

合肥远明科技有限公司

豪森国际(香港)有限公司天津分公司天津奥辛博科技有限责任公司

合肥原点生物科技有限公司


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目录

6 月 14 日晚主会场报告(20:00-21:20) .................................................................................. 13

单分子技术研究细胞膜结构和功能王宏达 ....................................................................... 13

Chemical Reaction Dynamics Studies of DNA G-Quadruplex 苏红梅 ................................. 14

6 月 15 日上午主会场报告（9:00-10:20） .......................................................................... 15

Spectroscopic Assessment of Protein Conformational and Hydration Dynamics 盖锋 ......... 15

利用原子力显微镜研究核酸-蛋白相互作用张文科 .......................................................... 16

6 月 15 日上午分会场报告 a（10:40-12:20） ..................................................................... 17

Developing New Tools and Probes to Visualize Chromatin Dynamics 孙育杰 ..................... 17

细胞原位磁性自旋成像王鹏飞 ........................................................................................... 18

Visualizing homology search with ssDNA curtains 齐志 , ReddingSy , LeeJayil , GibbBryan ,

KwonYoungHo , NiuHengyao , GainesWilliam , SungPatrick , GreeneEric .......................... 19

Imaging the cytoskeleton structure with super-resolution fluorescence microscope 钟桂生 . 20

6 月 15 日上午分会场报告 b（10:40-12:20） ..................................................................... 21

From Molecular Dynamics to Genomic Biology: Constructing Kinetic Network Models to

Elucidate Transcriptional Fidelity of RNA Polymerase II 黄旭辉 ......................................... 21

Genetic Incorporation of Unnatural Amino Acid as Protein Electron Transfer Probes 刘晓红

................................................................................................................................................ 22

超大蛋白质体系粗粒化的新方法夏飞 ............................................................................... 23

金属基纳米材料的电子特性与生物信号响应之间潜在关系研究张海元........................ 24

6 月 15 日上午分会场报告 c（10:40-12:20） ...................................................................... 25

Anomalous diffusion and dynamic disorder in biomolecular systems based on mesoscopic

statistical modeling 赵南蓉 .................................................................................................... 25

Structural modeling of proteins integrating small-angle X-ray scattering data 张泳辉，彭俊

辉，文彬，张志勇................................................................................................................. 27

Elucidation of Energy Transfer in the Photosystem II Reaction Center 张璐 ........................ 28

蛋白质静电和氢键作用的核磁共振研究张宁 , 李敬文 , 安辽原 , 姚礼山 ................... 29


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6 月 15 日下午主会场报告 .................................................................................................... 30

Dynamics and mechanism of ultrafast water-protein interactions 仲冬平 ............................. 30

Integrative Metallomic Approach to Match Metal to Proteins 孙红哲 1,2, Yau-Tsz Lai1, Ligang

Hu1,3, Yuen-Yan Chang1, 李洪艳 1, Yuchuan Wang2 .............................................................. 31

6 月 15 日下午分会场报告 a（15:40-17:20） ..................................................................... 32

Functional Photoactive Protein Synthesis Using Genetic Code Expansion 王江云 .............. 32

Synthesis, characterization and biological activities of a Valen Schiff base and its bismuth(III)

complex 李旭，李传华，蒋建宏，肖圣雄，李霞，张辉，李强国 .................................. 33

Position-dependent effects of ribose G-quartets in intramolecular G-quadruplex 周俊......... 34

Toll 样蛋白受体 13 的天然免疫识别和调控王晓辉 .......................................................... 35

6 月 15 日下午分会场报告 b（15:40-17:20） ..................................................................... 36

线粒体靶向药物刘义 , 樊晓阳 , 何欢 , 蒋风雷 ............................................................... 36

仿生纳米马达的构建及应用玄明君 , 戴陆如 , 贺强 , 李峻柏 ....................................... 37

仿生多尺度孔道的研究侯旭 ............................................................................................... 38

从原子的相互作用到细胞的恶性转变：多尺度方法研究慢性炎症-癌症相互关系的分子

机制廖结楼 ........................................................................................................................... 39

6 月 15 日下午分会场报告 c（15:40-17:20） ...................................................................... 40

The Sequence Preference in DNA Methylation Level and Its Structural Basis in Mammalian

高毅勤 , 张玲 , 古婵 ............................................................................................................ 40

红外光谱的检测灵敏度和选择性研究进展及其在生物体系中的应用张文凯 ,

MarkiewiczBeatrice , RodgersJeffrey , 陈建新 , 盖锋 ......................................................... 41

Ultrafast Dynamics in DNA Model System with Diverse Structures 陈缙泉 ........................ 42

Ion Effect on Hydrogen Bonding Network in Water 庄巍 ..................................................... 43

6 月 15 日晚上研究生报告专场 1（20:00-21:40） ............................................................. 44

A single-molecule study of diffusion of AlkD on dsDNA by FRET-FCS 潘白龙 , 赵新生 . 44

铜锌超氧化物歧化酶与 DNA 相互作用的热力学研究李享 , 刘长林 , 王珊珊 ............. 45

分子动力学模拟研究ANCA探针与Aβ纤维结合模式何欢，蒋风雷，刘义 ................... 46


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Kinetics study reveals the mechanism of the interaction between Cu(II) and Amyloid-β

peptides 李皓然 , 葛保胜 , 黄方 ......................................................................................... 47

Uncovering amyloid formation mechanism of yeast prion Ure2 by single molecule FRET and

kinetic analysis 杨洁， DearAlexander , KnowlesTuomas P.J. ，吴思， PerrettSarah ..... 48

6 月 15 日晚上研究生报告专场 2（20:00-21:40） ............................................................. 49

飞秒时间分辨和频光谱系统的发展与应用谈军军 ........................................................... 49

羧基取代偶氮苯类双亲分子的表面结构与组装特性研究夏文秀，胡中进，魏锋，ZhuXue

Feng，郑万泉 ........................................................................................................................ 50

于石墨烯量子点的功能性纳米荧光探针的构建以及在生物技术中的应用王雅楠 , 隋媛

红 , 王晓娟 , 黄方 ................................................................................................................ 51

基于荧光乙二醇壳聚糖衍生物的脂筏原位成像蒋耀文 , 郭皓月 , 吴富根 ................... 52

基于 DNA 和金属离子特异性作用的多输入分子逻辑门李菁菁 ..................................... 53

6 月 15 日晚上研究生报告专场 3（20:00-21:40） ............................................................. 54

Motions of Allosteric and Orthosteric Ligand Binding Sites in Proteins are Highly Correlated

马晓旻，孟虎，来鲁华 ......................................................................................................... 54

Tertiary Structure Formation in Simian Retrovirus Type 1 RNA Pseudoknot Increases

Mechanical Stability and −1 Ribosomal Frameshifting Efficiency 钟振声, 杨丽霞 , 陈刚 55

Direct observation and ligand regulation of oligomeric state of CXCR4-EGFP on the

membrane of living cells 劳军，songyanzhuo，葛保胜，黄方，HeHua ........................... 56

两种金属钌配合物的设计合成及其与 DNA 的相互作用研究尹盼盼 ............................. 57

生物膜界面化层层组装微胶囊邵婧鑫 , 戴陆如 , 贺强 ................................................... 58

6 月 16 日下午主会场报告（8:30-9:50） ............................................................................ 59

Vinculin mediated mechanosensing at focal adhesions 严洁 ................................................. 59

Kinetic rates versus quantum dissipation 严以京 .................................................................. 60

6 月 16 日上午分会场报告 a（10:10-12:10） ..................................................................... 61

肝脏免疫的力学-化学耦合龙勉、章燕、吕守芹、李宁 .................................................. 61

RHAU解旋酶水解ATP解链G-四链体DNA的工作机制的研究游慧娟, LattmannSimon ,

RhodesDaniela , 严洁............................................................................................................. 62

肿瘤治疗过程中细胞迁移的生物力学研究姚立 ............................................................... 63


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单分子力谱技术检测凝集素与细胞表面糖之间的相互作用蔡明军 , 赵伟栋 , 徐海娇 ,

蒋俊光 , 王宏达 .................................................................................................................... 64

用单分子荧光手段阐释翻译过程动力学及分子机制陈春来 ........................................... 65

6 月 16 日上午分会场报告 b（10:10-12:10） ..................................................................... 66

利用 DNA 组装结构调控酶级联反应刘冬生 ..................................................................... 66

Effect of Molecular Geometry on the Self-Assembly of Peptide Isomers and Their Application

as DNA Vectors 曹美文 , 赵文静，谢子龙，徐海 ............................................................. 67

软物质纳米组装体的亚细胞定位机制吴富根 , 贾浩然 , 王宏银 , 李艳红 , 蒋耀文 ,

陈晓凯 , 潘光玉 , ChenZhan ................................................................................................ 68

含核苷类抗癌药物 DNA 纳米结构的构建及其与细胞相互作用张川 ............................. 69

基于自然纤维素物质的仿生纳米材料用作锂离子电池电极的研究黄建国.................... 70

6 月 16 日上午分会场报告 c（10:10-12:10） ...................................................................... 71

超分辨率活细胞成像技术进展李栋 ................................................................................... 71

化学交联质谱分析用于蛋白质动态结构的研究刘主 ....................................................... 72

核酸分子-细胞膜作用过程中磷脂双层膜的电荷反转与重构魏锋 , 李雯慧 , 郑万泉 .. 73

Computational design of peptide-Au cluster probe for αIIbβ3 integrin detection and

quantification in single cells 赵丽娜 ...................................................................................... 74

上转换荧光分析方法及生物应用李贞 , 刘志洪 ............................................................... 75

6 月 16 日下午分会场报告 a（14:00-16:00） ..................................................................... 76

Protein dynamical structures and their relevance to biological function revealed by

time-resolved temperature-jump transient IR spectroscopy 翁宇翔 ................................... 76

Studies on Conformation changes of biomolecules by Terahertz time-domain spectroscopy 颜

识涵 , 张明焜 , 魏东山 ........................................................................................................ 77

微流控芯片高通量单细胞分泌蛋白分析陆瑶，FANRONG ............................................ 78

溶液顺磁弛豫增强用于蛋白质结构和动态学研究龚洲 , 顾新华 , 唐淳 ....................... 79

界面生物分子相互作用及界面振动能量传递叶树集 ....................................................... 80

6 月 16 日下午分会场报告 b（14:00-16:00） ..................................................................... 81


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Insight into the Binding of Metal Ions and Small Bioactive Molecules with

Bio-macromolecules through Crystallography 王宏飞，王文明，ZhangXinyu , PanHuifen ,

MaZhiou , XuLiqun ................................................................................................................ 81

Conjugated Polymer Grafted with H2O2-Sensitive Prodrug for Cell Imaging and Tumor Cell

Killing 刘礼兵，李梦，吕凤婷，王树 ................................................................................ 82

Structural and functional of Hantavirus nucleocapsid proteins 郭宇 , 王文明 ................... 83

Ultrastructure and mechanical perturbation of pulmonary surfactants by inhaled carbon

nanoparticles: a computer simulation study 岳同涛 , 黄方 , 徐燕 ...................................... 84

Probing protein conformational dynamics by combining experimental and computational

studies 王文宁 ........................................................................................................................ 85

6 月 16 日下午分会场报告 c（14:00-16:00） ...................................................................... 86

蛋白质别构调控分子设计来鲁华 ....................................................................................... 86

Decoding Collagen - Computational Design of Fibrous Proteins 许菲 ................................. 87

Developing RNA Duplex-Binding Peptide Nucleic Acids for Biotechnological Applications

陈刚 ........................................................................................................................................ 88

基于弱相互作用的蛋白质-多糖特异性识别机理的分子模拟研究康玉 .......................... 89

基于人工设计蛋白研究折叠协同性等序列结构规律刘海燕 ........................................... 90

6 月 17 日上午分会场报告 a（8:30-10:10） ....................................................................... 91

Genetically-encoded Voltage Indicators Based on Electrochromic FRET 邹鹏 .................... 91

白细胞细胞骨架动态重组的分子机制及数值模拟冯世亮 , 章燕 , 龙勉 ....................... 92

Super-resolution imaging and reconstructions of chromosome architecture in yeast and human

cell 郝先 , WeberChristian , OuyangWei , ZimmerChristophe .............................................. 93

Single-Molecule Study Reveals Reactive Oxygen Species mediate BIN2's activity in

Brassinosteroids Signaling Pathway 谭砚文 .......................................................................... 94

6 月 17 日上午分会场报告 b（8:30-10:10） ....................................................................... 95

Visualizing protein excited-state structures with conjoint use of biophysical techniques 唐淳

................................................................................................................................................ 95

真核七次跨膜蛋白Leptosphaeria rhodopsin结构和机理的固体核磁共振研究王申林，

LiuJing , LiuChang ................................................................................................................. 96

水通道蛋白 AqpZ 结构及功能的固体 NMR 研究赵永祥 ................................................. 97


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基于钻石探针的单分子磁共振波谱新技术石发展 ........................................................... 98

6 月 17 日上午分会场报告 c（8:30-10:10） ........................................................................ 99

A Microfluidic Device Integrating Size Based Separation and Affinity Capturing for

Synergistic Enrichment of Circulating Tumor Cells 杨朝勇 ................................................. 99

二维纳米芯片模板上 DNA 级联机器模拟分子水平信号传导及其应用柳华杰 ........... 100

基于细胞分群计数的白细胞荧光染色平衡研究高婷娟 ................................................. 101

分子伴侣辅助的膜蛋白折叠研究黄方 ............................................................................. 102

6 月 17 日上午主会场报告（10:30-11:10） ....................................................................... 103

高效靶向端粒酶和淀粉样蛋白及其作用机制的新进展曲晓刚 ..................................... 103

墙报摘要（按照墙报提交先后顺序） ............................................................................... 104

红外光谱的检测灵敏度和选择性研究进展及其在生物体系中的应用张文凯 ,

MarkiewiczBeatrice , RodgersJeffrey , 陈建新 , 盖锋 ....................................................... 104

Nanoparticle-Biomembrane Interactions Investigated by In Situ Surface Nonlinear

Spectroscopy 陆洲 ............................................................................................................... 105

基于超分子自组装原理的“杀菌开关” 白昊天 , 王树 ...................................................... 106

Synthesis of a Novel Quinoline Skeleton Introduced Cationic Polyfluorene Derivative for

Multimodal Antimicrobial Application 孙含 ....................................................................... 107

基于水溶性共轭聚合物的病原菌检测、杀伤以及抗菌敏感性的评价及抗生素的筛选研究

王耀坤 .................................................................................................................................. 108

疏水单元对i-motif DNA二级结构稳定性的研究孙亚伟，徐海 ..................................... 109

一种改进的副本交换方法陈长军 ..................................................................................... 110

自驱动胶体马达：可控分子组装，理论模拟及生物医学应用贺强 , 志光吴 , 司铁岩 ,

林显坤 .................................................................................................................................. 111

阳离子OPV用于光拮抗细胞耐药性研究周鑫 , 吕凤婷 , 刘礼兵 , 王树 ..................... 112

3-羟基黄酮类 Zn2+荧光探针的设计、合成及其在前列腺癌细胞识别上的应用徐玉林 ,

李节 , 刘长林 ...................................................................................................................... 113

共轭聚合物—纳米银复合体系在无标记蛋白检测中的应用王晓瑜 , 李盛亮 , 张鹏博 ,

王树 ...................................................................................................................................... 114

Cationic Conjugated Polymers-Induced Quorum Sensing of Bacteria Cells 张鹏博 .......... 115


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聚合物纳米粒子的制备及其细胞膜成像研究贺萍 , 李梦 , 刘礼兵 , 吕凤婷 , 王树 . 116

A Fluorescence Ratiometric Assay Strategy for Chemical Transmitter of Living Cells Using

H2O2 – Sensitive Conjugated Polymers 王云侠 ................................................................. 117

模拟细胞膜体系制备及应用韩晓军 ................................................................................. 118

姜黄素与 CopC 相互作用的光谱研究宋珍，lubaoping ，杨斌盛................................. 119

具有活性氧自清除能力的聚噻吩在细胞成像中的应用陈艳艳 , 胡蓉 , 吕凤婷 , 刘礼

兵 , 王树 .............................................................................................................................. 120

聚噻吩-DNA 杂化水凝胶的制备及细胞捕获、杀伤研究卢欢 ....................................... 121

pH 值响应的共轭聚合物纳米粒子的制备、表征与细胞成像研究王建武 .................... 122

基于氧化石墨烯/共轭聚合物复合材料的蛋白检测和功能调控研究邢成芬 , 范一冰 ,

柴燃 ...................................................................................................................................... 123

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the

Mechanism for Ribonucleoprotein Complex Formation 王文明 , 郭宇 ............................. 124

Conjugated Polythiophene for Rapid, Simple and High-Throughput Screening of

Antimicrobial Photosensitizers 牛瑞民 , 邢成芬 , 李瑞华 ............................................... 125

水溶性石墨烯量子点的合成与表征高天，刘义 ............................................................. 126

银原子簇对大肠杆菌抗菌活性的研究金建成 , 吴小娟 , 王贝贝 , 蒋风雷 , 刘义 ..... 127

Photosynthesis Controlled Detection of Carbon Dioxide Base on Guanidinium Pendant

Oligofluorene 邢成芬 , 袁宏博 , 范一冰 .......................................................................... 128

Location, Function and Structural Dynamics of a Vibrational Marker in a Photoactive Protein

王建平，于鹏云，杨帆 ....................................................................................................... 129

NO、O2 铁卟啉键合产物研究进展—晶体结构与化学键振动李剑峰 .......................... 130

石墨烯量子点的离子响应王晞 , 高天 , 巴晓旭 , 刘义 ................................................. 131

用于胞内 GSH 检测的水溶性“off-on”荧光探针性能研究黄蓉 ...................................... 132

等温滴定量热在蛋白纤维化研究中的应用杨琪琦 , 张嘉淇 , 刘义 ............................. 133

In vitro effect of nicotine on isolated mitochondria studied by spectroscopic and microscopic

methods LiuJun-Yi , ZhangYue ,马龙，蒋风雷 ................................................................... 134

Development of a Refined Benchmark for Assessing Scoring Functions Used in

Protein-Protein Docking 韩莉，刘志海，李嫣，李婕，王任小 ...................................... 135


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有机胂化合物引起线粒体 Ca2+依赖的膜渗透性转换孔的开放樊晓阳 , 刘玉娇 , 刘义

.............................................................................................................................................. 136

荧光金纳米团簇与蛋白质相互作用的热力学基础尹苗苗 ............................................. 137

靶向天然无序蛋白的理性药物设计阮浩 , 余辰 , 来鲁华 ............................................. 138

Probing Conformational and Electronic Changes in Redox Proteins with Electrochemical

Surface Plasmon Resonance Dr. TJ Jing ............................................................................... 139

胆固醇在生物膜中的传输与组装的和频光谱研究郁婷 , 叶树集 ................................. 140

F16 类有机胂化合物对细胞凋亡的探究刘玉娇 .............................................................. 141

量热法测量氯已定对白色念珠菌生长代谢的影响徐娟 , 刘义 , 蒋风雷 ..................... 142

Computational Design of Fibrous Proteins 许菲.................................................................. 143

不同配体修饰 CdTe 量子点对线粒体渗透转换孔的影响向迅 , 蒋风雷 ....................... 144

三种亲脂性阳离子线粒体靶向性能研究高涛 , 向讯 , 蒋风雷 , 刘义 ......................... 145

Temperature effect on the dynamics of fluorescence probe for specific detection of cysteine 王

芳芳，蒋风雷，刘义........................................................................................................... 146

pH-induced conformational isomerization of colicin A pore forming domain 黄艳 , 樊俊鹏 ,

LakeyJeremy , 刘义 ............................................................................................................. 147

界面蛋白质-蛋白质与蛋白质-磷脂相互作用的非线性光谱识别张柏雄 , 叶树集 , 罗毅

.............................................................................................................................................. 148

金属镉离子结合蛋白生物传感器的理性设计李烆一 , 张长胜 , 来鲁华 ..................... 149

Single-molecule and ensemble FRET reveals the conformational heterogeneity and allosteric

mechanism of human Hsp70 吴思, HongLiu , 杨洁 , YangJie , ZhangHong , PerrettSarah

.............................................................................................................................................. 150

生物钟网络小分子调节剂的设计与发现解晓雯 ............................................................. 151

Thermodynamic and kinetic observation of transmembrane segments of CXCR4 binding to

GroEL 迟海霞，王小强，李世新，任浩，徐燕，黄方 .................................................. 152

Ultrastructure perturbation of pulmonary surfactant monolayers by inhaled single-walled

carbon nanotubes with defined aspect ratio and surface pattern: internalization pathways 徐燕，

岳同涛，黄方 ...................................................................................................................... 153

Molecular Modeling of Interplay between Nanoparticle Wrapping and Clustering of Inner

Anchored Membrane Proteins 李世新，岳同涛，黄方 ..................................................... 154


11

Combinational biosynthesis of novel dual-functional phycobiliproteins and its application in

early diagnosis of liver cancer 吝晓君 , 王祥法 , 葛保胜 , 黄方 .................................... 155

基于多巴胺受体蛋白结构中的分子通道理论透视帕金森病病理徐四川...................... 156

多态性蛋白Mad2折叠与功能的研究张会亭 , 黄方 , 赵园园 ........................................ 157

《Kinetic and thermodynamic studies reveal chemokine homologues CCL11 and CCL24 fold

differently》孙婷婷，葛保胜，黄方 ................................................................................ 158

Tracking live cell membrane invagination of the single virion by force tracing based on atomic

force microscopy 单玉萍，王宏达 ..................................................................................... 159

X-ray Crystallography Applied in Nucleotide-Transition Metal Coordination Complexes 李晖，

仇启明 .................................................................................................................................. 160

Femtosecond laser-induced nano-explosion for the destruction of amyloid-beta fibrils with

gold nanorods 林冬冬，HeRuoyu , 杨新菊 ....................................................................... 161

水溶性阳离子共轭聚合物的细胞成像和基因递送研究李盛亮 , 吕凤婷 , 刘礼兵 , 王

树 .......................................................................................................................................... 162

转录因子与 DNA 相互作用调控机制的分子动力学模拟研究高军 , 熊乐 , 李根 ....... 163

AutoT&T v.2: An Efficient and Versatile Tool for Lead Structure Generation and Optimization

王任小 .................................................................................................................................. 164

水溶性寡聚苯撑乙烯在克服肿瘤细胞耐药性方面的设计与研究周凌云...................... 165

Research on Aggregation of Human Chemokine Receptor CCR3 李计强，ZhouShitan ,葛保

胜，黄方 .............................................................................................................................. 166

Effect of calcium ions on the nanostiffness of articular cartilage 庞祥超 , 唐斌 ................ 167

The crystal structure of the respective permease YknZ extracellular domain from Bacillus

amyloliquefaciens 许永斌 .................................................................................................... 168

RGD多肽靶向的超支化聚乙烯亚胺纳米探针的制备及其肝肿瘤SPECT/CT双模态诊断

周本青 , 史向阳 , 王瑞芝 , 王小林 .................................................................................. 169

基于环糊精的多价态结合抗血栓药物载体的设计李莉 ................................................. 170

Non-B DNA/卟啉类配体相互作用的瞬态光谱研究秦廷箫 , 宋迪 , 刘坤辉 , 苏红梅 171

The transient ion-pair species captured in the oxidation process of DNA Guanine 节家龙 , 刘

坤辉 , 苏红梅 ...................................................................................................................... 172

A “Flip-Flop” Mechanism of a Double-Helix Foldamer’s Disassembly 赵东波，DongHao ,

LiShuhua ............................................................................................................................... 173


12

A multifunctional targeted MRI/CT dual-mode imaging probe for cancer diagnosis and in situ

real-time treatment 岳鲁丹，WANGJinlong , 郑秀文 ....................................................... 174

探讨白细胞介素IL-21特殊抗体提升机体免疫力的机理崔艳芳 , 梅龙灿 , 耿晖 ........ 175

Binding to bovine serum albumin protects β-carotene against oxidative degradation 常慧婷，

张建平 .................................................................................................................................. 176

OmpC is expansive with the help of chaperone SurA 李耕 ................................................. 177

Scanning single-molecule fluorescence correlation spectroscopy enables kinetics study from

microseconds to seconds 毕慧敏 ......................................................................................... 178

Molecular Dynamic Simulations of the Trp-cage Folding/unfolding Mechanism and its

Folding-related Problems Based on PDB Coil Library 吴晓敏，张海军 ........................... 179

PEI–folic acid modi fied carbon nanodots for cancer cell-targeted delivery and two-photon

excitation imaging 王晶 ....................................................................................................... 180

Understanding GPCR diversity and ligand specificity from the big data in virtual screening 周

庆同 , 赵素文 ...................................................................................................................... 181

smFRET study of interaction between M.HhaI and dsDNA 何姗珊 ................................... 182

Detection of bound chaperones by single-molecule FCS 潘思辰 , 赵新生 ........................ 183

Thermochromatium

tepidum外周捕光天线蛋白LH2在脂质体及表面活性剂胶束中的光谱性质对比王鹏 ,

霍一林 , 张建平 .................................................................................................................. 184

β-胡萝卜素聚集体制备及其光物理性质研究张迪 , 王鹏 .............................................. 185

Dispersed OmpT may be partially folded 卜佩璇，赵新生 ................................................ 186

Tertiary Structure Formation in SRV-1 RNA Pseudoknot Increases Mechanical Stability and

−1 Ribosomal Frameshifting Efficiency 钟振声，杨丽霞，陈刚 ...................................... 187

附：参会人员名录（会前注册版） ................................................................................... 188


13

6 月 14 日晚主会场报告(20:00-21:20)

单分子技术研究细胞膜结构和功能

王宏达

中国科学院长春应用化学研究所

摘要

细胞膜是高等生命体基本结构单元“细胞”的天然屏障，它把细胞与外界环境分离开来。细胞膜有许多重要

的生物功能，如物质隔离、物质交换和细胞通讯等。在分子水平研究细胞膜的结构对解释细胞膜的功能和

治疗细胞膜相关疾病有重要的指导意义。细胞膜结构研究已经有近百年的历史；然而由于结构复杂、研究

条件有限，细胞膜这一超分子结构尚处在模型假说阶段。我们利用多种单分子技术（原子力显微镜、超分

辨荧光显微镜和单分子力谱技术）在接近生理条件下对多种细胞膜（包括血红细胞膜、细胞器膜和哺乳动

物有核体细胞膜等）进行了深入系统的研究，从整体角度揭示了细胞膜的非对称性和种类差异性，并提出

了红细胞的“半镶嵌”模型（Semi-mosaic Model）和哺乳动物组织细胞的“蛋白层-磷脂-蛋白岛”模型（Protein

Layer-Lipid-Protein Island model）；同时，利用单分子力谱和力示踪技术记录了单分子/单颗粒跨膜转运的

动态过程。

关键字:细胞膜,原子力显微镜,超分辨荧光显微镜,单分子力谱技术


14

Chemical Reaction Dynamics Studies of DNA G-Quadruplex

苏红梅

北师大化学学院

摘要

G-quadruplexes are tetrastranded helices structures arising from the self-assembly of specific guanine-rich DNA

sequences, which exist ubiquitously in human genome including the telomere as well as promoter regions of

certain oncogenes. Recent studies demonstrate the formation of G-quadruplex structures not only in vitro, but also

in human cells. G-quadruplex DNA have attracted intense research interests in respect of their biological role, as

targets for anticancer therapy and, more recently, of their potential applications in the field of molecular

electronics. Here we report our studies on the chemical reaction dynamics of DNA G-quadruplex by means of

transient absorption spectroscopy, including the examination of the G-quadruplex/ligand interaction, the direct

observation and findings of the unique deprotonation pathways of the one-electron loss centers (holes) within

G-quadruplex structures that is important for DNA-mediated charge transfer, and some newly obtained results for

the capture of a crucial radical ion-pair intermediate involved in the DNA oxidative damage reactions.

关键字:deprotonation following one-electron oxidation,radical ion-pair intermediate


15

6 月 15 日上午主会场报告（9:00-10:20）

Spectroscopic Assessment of Protein Conformational and Hydration

Dynamics

盖锋

University of Pennsylvania

摘要

Proteins are flexible and dynamic polymers, necessitating various motions that are required for function. However,

experimental assessment of protein conformational dynamics, especially those underlying protein functions, is

challenging. This is because a protein’s conformational transition can occur either locally or globally and on a

wide range of timescales. In this talk, we will discuss how different spectroscopic methods can be combined to

overcome this difficulty, using the M2 proton channel of the Influenza A virus as an example.

关键字:Spectroscopy,Dynamics


16

利用原子力显微镜研究核酸-蛋白相互作用

张文科

吉林大学

摘要

原子力显微镜技术（AFM）的出现使得对生物大分子的单分子观测及操纵成为可能[1,2]。AFM 友好的工作

环境（比如，可以在溶液中工作）使得无论是空气中或者溶液中的高精度成像都可以实现。基于原子力显

微镜技术的单分子力学谱（以下简称单分子力谱）的出现使得人们能够对单个大分子进行力学操纵和加工，

从而对分子结构与构象变化，分子间的相互作用以及反应历程实现单分子水平的实时-原位观测。通过传统

的 AFM 成像，可以实现对分子间作用模式（或者结合过程）的直观检测，而利用 AFM 力谱方法可以实现

对分子间（或分子内）作用强度的定量检测。目前 AFM 已经成为生物物理，高分子科学，表面科学和细

胞分子生物学等领域不可或缺的一种重要的研究手段[3-7]。核酸与蛋白质的相互作用贯穿于分子生物学中

心法则的每一个环节，在单分子水平对这些蛋白质与核酸的作用机理以及相互作用的影响因素的研究，有

助于深化人们对 DNA 复制（或者病毒复制、感染）等重要生命过程发生的分子机理的认识，从而为最终

实现对 DNA 复制等过程的人为调控奠定基础[7c-7e]。本次报告将首先介绍如何利用 AFM 成像静态研究核

酸与蛋白质之间的相互作用，然后以 PcrA 解旋酶为例讲述 AFM 成像原位观测该分子马达对 DNA 片段的

搬运作用。接下来将介绍双螺旋 DNA 的力学指纹谱、外力诱导下 DNA 构象转变的本质以及如何利用该力

学指纹谱研究 DNA 结合蛋白等与 DNA 的相互作用。最后，我们以烟草花叶病毒为例，探索单分子力谱在

研究复杂体系中核酸-蛋白质相互以及揭示病毒感染过程中解组装机理作用中的应用。参考文献： 1. Binnig,

G.; Quate, C. F.; Gerber, C. Phys. Rev. Lett., 1986, 56:930-33. 2. Hansma, H. G. Annu. Rev. Phys. Chem., 2001,

52:71–92 3. Müller, D. J.; Dufrêne, Y. F. Nat. Nanotechnol., 2008, 3: 261-269. 4. Kufer, S.; Puchner, E.; Gumpp,

H.; Liedl, T.; Gaub, H. E. Science, 2008, 319:594-596. 5. Merkel, R. Phys. Rep., 2001, 346: 343–385. 6.

Clausen-Schaumann, H.; Seitz, M.; Krautbauer, R.; Gaub, H. E. Curr. Opin. Chem. Biol., 2000, 4: 524–530. 7. (a)

Zhang, W. K.; Zhang, X. Prog. Polym. Sci., 2003, 28: 1271–1295. (b) Zhang, W.; Barbagallo, R.; Madden, C.;

Roberts, C.J.; Woolford, A.; Allen, S. Nanotechnol., 2005, 16: 2325-2333. (c) Zhang, W.; Carneiro, M.J.V.M.;

Turner, I.J.; Allen, S.; Roberts, C.J.; Soultanas, P. J. Mol. Biol., 2005, 351: 66-75. (d) Zhang, W. K.; Dillingham,

M. S.; Thomas, C. D.; Allen, S.; Roberts; C. J.; Soultanas, P. J. Mol. Biol., 2007, 371: 336-348. (e) Zhang, W. K.;

Machon, C.; Orta, A.; Phillips, N.; Roberts, C. J.; Allen, S.; Soultanas, P. J. Mol. Biol., 2008, 377: 706-714. (f) Liu,

N. N.; Bu, T. J.; Song, Y.; Zhang, W.; Li, J. J.; Zhang, W. K.; Shen, J. C.; Li, H. B. Langmuir, 2010, 26:

9491-9496. (g) Liu, N. N.; Peng, B.; Lin, Y.; Su, Z. H.; Niu, Z. W.; Wang, Q.; Zhang, W. K.; Li, H. B.; Shen, J. C.

J. Am. Chem. Soc., 2010, 132: 11036-11038. (h) Liu, N. N.; Chen, Y.; Peng, B.; Lin, Y.; Wang, Q.; Su, Z. H.;

Zhang, W. K.; Li, H. B.; Shen, J. C. Biophys. J., 2013, 105: 2790-2800. (i) Xue, Y. R.; Li, X.; Li, H. B.; Shen, J. C.

Nat. Commun., 2014, 5:4348. (j) Chen, Y.; Ma, K.; Hu, T.; Jiang, B.; Xu, B.; Tian, W. J.; Sun, J-Z.; Zhang, W. K.

Nanoscale, 2015, 7: 8939-8945.

关键字:原子力显微镜,单分子力谱,核酸-蛋白相互作用,病毒解组装


17

6 月 15 日上午分会场报告 a（10:40-12:20）

Developing New Tools and Probes to Visualize Chromatin Dynamics

孙育杰

BIOPIC, School of Life Sciences, Peking University, Beijing China

摘要

Cell nucleus is highly crowded yet organized. Essential biological processes are tightly regulated in time and space.

We apply single molecule and super-resolution imaging techniques to understand the spatial-temporal

regulation of nuclear structure and dynamics.


18

细胞原位磁性自旋成像

王鹏飞

中国科学技术大学

摘要

基于自旋的蛋白质成像是非常重要的，特别是在细胞原位,可以防止离体蛋白出现的一些信息丢失。然而现

有的技术方法却难以实现。我们使用金刚石中的固态单自旋传感器，演示了室温大气下细胞原位的基于自

旋的蛋白质的成像。使用生物学上细胞包埋的方法，保证了其中铁蛋白的原位信息，最终得到了细胞内的

铁蛋白团簇的图像。这种技术让我们可以从细胞原位上纳米尺度研使用磁共振成像手段研究细胞的生理机

制。

关键字:细胞原位,成像,自旋,金刚石固态自旋传感器


19

Visualizing homology search with ssDNA curtains

齐志 , ReddingSy , LeeJayil , GibbBryan , KwonYoungHo , NiuHengyao ,

GainesWilliam , SungPatrick , GreeneEric

Peking University

University of California, San Francisco

Columbia University

Columbia University

Yale University

Indiana University

Yale University

Yale University

Columbia University

摘要

Homologous recombination (HR) mediates the exchange of genetic information between sister or homologous

chromatids. During HR, members of the RecA/Rad51 family of recombinases, like scRad51, hRad51, RecA, and

scDmc1, must align and pair single-stranded DNA (ssDNA) with a homologous dsDNA template, but the physical

basis for these early stages of recombination remain largely undefined. Here we use ssDNA-curtains to visualize

RecA/Rad51 family members as they align and pair homologous DNA sequences in real-time. We find

microhomology sampling is the key point to understand homology search: (1) During interrogating dsDNA,

RecA/Rad51 family members enable robust kinetic selection of 8-nt tracts of microhomology, which kinetically

confines the search to sites with a high probability of being a homologous target; (2) RecA/Rad51 family members

rapidly sample and reject dsDNA with < 8-nt tracts of microhomology through a mechanism characterized by its

distinctive power-law dependence; (3) Successful pairing with a 9th nucleotide coincides with an additional

reduction in binding free energy and subsequent strand exchange occurs in precise 3-nt steps, reflecting the base

triplet organization of the presynaptic complex; (4) dsDNA binding on the presynaptic complex by a short length

of microhomology can be disrupted by other dsDNA molecules with an equal or longer microhomology length.

This process is termed facilitated exchange, and it depends on the microhomology length and sequence. These

findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination.

关键字 :Single-molecule biophysics,DNA curtains,Homologous recombination,Total internal reflection

fluorescence microscopy


20

Imaging the cytoskeleton structure with super-resolution fluorescence

microscope

钟桂生

IHuman Institute and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China

摘要

Fluorescence microscope is a widely used technology in biology and medicine because of its specificity,

labeling efficiency, and the capability of live cell imaging. However, due to the light diffraction, the spatial

resolution of fluorescence microscope is limited by the used light and is around 250nm. Many important questions

in biology and medicine was still obscured because of the lack of proper imaging tools. In this talk, I will introduce

the concept of super-resolution fluorescence microscope and discuss the different ways to achieve the spatial

super-resolution. Then I will talk the recent progress that has been made by super-resolution fluorescence

microscope technology and the preliminary results from my lab. We recently found some interesting cytoskeleton

structure from hair cells in the auditory system. With further development of better probes, we expect more

important findings in both biology and medical science fields by super-resolution fluorescence microscope.


21

6 月 15 日上午分会场报告 b（10:40-12:20）

From Molecular Dynamics to Genomic Biology: Constructing Kinetic

Network Models to Elucidate Transcriptional Fidelity of RNA Polymerase II

黄旭辉

The Hong Kong University of Science and Technology

摘要

Transcription, the synthesis of RNA from a complementary DNA template, plays a crucial role in cellular

regulation, including differentiation, development, and other fundamental processes. In this talk, I will discuss our

results on modeling the RNA polymerase II (Pol II, a system with ~400K atoms) Translocation and other

functional conformational changes of this enzyme at sub-millisecond timescales. We have developed a novel

algorithm, Hierarchical Nystrom Extension Graph method, to construct kinetic network models to extract long

timescale dynamics from short simulations. For example, we reveal that RNA polymerase II translocation is driven

purely by thermal energy and does not require the input of any additional chemical energy. Our model shows an

important role for the bridge helix: Large thermal oscillations of this structural element facilitate the translocation

by specific interactions that lower the free-energy barriers between four metastable states. The dynamic view of

translocation presented in our study represents a substantial advance over the current understanding based on the

static snapshots provided by X-ray structures of transcribing complexes. At the end of my talk, I will briefly

discuss our recent progress on extending our kinetic network model to include sequence-dependent molecular

dynamics of Pol II elongation to predict transcriptional accuracy in the genome-wide transcriptomic datasets. This

model creates a critical link between the structural-mechanics understanding of Pol II fidelity and the

genome-wide transcriptional accuracy.

关键字:Molecular Dynamics,Gene Transcription,Markov State Model


22

Genetic Incorporation of Unnatural Amino Acid as Protein Electron Transfer

Probes

刘晓红

中国科学院生物物理研究所

摘要

Electron transfer (ET) reactions govern many important biochemical processes, including oxygen binding,

photosynthesis, respiration, and detoxification. Efficient photo-induced electron transfer (PET) typically requires

close proximity of the donor and acceptor. The PET method nicely complements FRET studies for the

investigation of small-scale conformation changes in biopolymers. By using of genetic incorporation of unnatural

amino acids (UAA), several UAAs can be site-specifically incorporated into fluorescent proteins. We showed that

PET from the chromophore to UAA or their metal complex can occur rapidly, suggesting that the fluorescent

proteins may be optimized for the ET reaction. By substituting Tyr of the chromophore in diverse FPs with HqAla,

we show for the first time UAA incorporation result in significantly red-shifted excitation and emission maxima.

Such red-shifted GFP variants are extremely useful for tracking protein localization in cells, deep-tissue imaging,

and the construction of fluorescence resonance energy transfer (FRET) sensors for a host of signaling molecules

and post-translational modifications. These new genetically encoded amino acids could also aid the rational design

of metalloproteins, as well as protein NMR spectroscopy using paramagnetic ions.

关键字:Electron transfer,Genetic incorporation,UAA


23

超大蛋白质体系粗粒化的新方法

夏飞

East China Normal University

摘要

模拟蛋白质大体系功能的有效手段之一是发展相应的粗粒化模型(Coarse-Grained Model)，确定其体系的粗

粒化划分需要建立严格系统的方法。我们最近提出了一种称为“波动极大化粗粒化”(FM-CG)的新方法，该

方法主要通过极大化蛋白质体系中各个功能区域间的相对波动来确定体系的粗粒化粒子的划分。同时，我

们发展了一种称为“分步局域迭代优化”(SLIO)的算法来加速蛋白质大体系的粗粒化划分过程，该算法最大

的优点在于，不但能够得到与模拟退火近似的结果，并且计算速度比模拟退火快两个数量级以上。我们对

一系列蛋白质大体系的测试结果表明，对于含有上千个残基的体系，利用弹性网络模型作为细粒化模型进

行粗粒化所需的时间在“秒”的时间尺度内，远远少于模拟退火所用的时间。

关键字:粗粒化新方法,超大体系


24

金属基纳米材料的电子特性与生物信号响应之间潜在关系研究

张海元

中国科学院长春应用化学研究所

摘要

金属基纳米材料以其独特的物理化学性质及超高的产量成为纳米材料在工业界及与人类生活息息相关领域

应用的典范。在纳米-生物界面水平理解这些纳米材料的物理化学属性与其引发的生物活性之间的属性-活

性关系将有助于深入了解纳米材料生物效应、预测未知纳米材料的安全性及对危险性纳米材料进行安全性

重新设计。金属基纳米材料往往区别于其他种类纳米材料而展露出独特的物理化学属性，其中的能级特性、

表面异质结构和活性晶面常常赋予纳米材料超高的表面活性，能够引发细胞的氧化性应激，导致 GSH 水平

的降低、ROS 升高、二相酶的表达及线粒体功能障碍，破坏多种组织和细胞器的功能，引起严重的毒性。

安全性设计策略致力于通过控制金属基纳米材料的制备条件和后处理方式来对危险性的物理化学属性进行

改造，从而获得安全的纳米材料。微量元素掺杂及表面卤素后处理被发现能够很好的改造这些物理化学属

性，从而降低金属基纳米材料的毒性，推动纳米材料的进一步广泛应用。

关键字:金属基纳米材料,物理化学属性,生物活性


25

6 月 15 日上午分会场报告 c（10:40-12:20）

Anomalous diffusion and dynamic disorder in biomolecular systems based

on mesoscopic statistical modeling

赵南蓉

四川大学化学学院

摘要

In this talk, I will present three relevant topics concerning anomalous diffusion of nanoparticles proteins in

polymer solutions, dynamic disorder effect in single molecule pulling experiments as well as non-exponential

kinetics of DNA transport through bimolecular nanopores . Firstly, I will talk about diffusion of nanoparticles in

semidilute polymer solutions based on mode-coupling theory study. We proposed a theoretical formalism to study

the long-time diffusion behavior of nanoparticles in polymer solutions by using mode-coupling theory (MCT). The

non-hydrodynamic part of the total diffusion coefficient D is calculated in the MCT framework where the polymer

dynamic scattering function in the solution plays an important role. We compute D straightforwardly and

investigate explicitly how D depends on the volume fraction of the polymer solution, the nanoparticle size, the

degree of polymerization, as well as the entanglement effects. For illustration, we adopt our theoretical approach to

analyze the diffusion of gold nanoparticles in semidilute poly(ethylene glycol) (PEG)-water solutions which has

been studied in detail experimentally. We found that our theoretical results show very good quantitative

agreements with the experimental data in many aspects, such as the strong dependence on volume fraction, the

large deviation from Stokes-Einstein relation particularly for small particles, as well as the effects of the PEG

molecular weight. Such good agreements clearly demonstrate the validity of our MCT framework, which may

serve as a good starting point to study many more complex dynamical behaviors associated with polymer solutions.

Secondly, I will talk about the kinetics of molecular transitions with dynamic disorder in single-molecule pulling

experiments. Macromolecular transitions are subject to large fluctuations of rate constant, termed as dynamic

disorder. The individual or intrinsic transition rates and activation free energies can be extracted from

single-molecule pulling experiments. We present a theoretical framework based on a generalized Langevin

equation with fractional Gaussian noise and power-law memory kernel to study the kinetics of macromolecular

transitions to address the effects of dynamic disorder on barrier-crossing kinetics under external pulling force. By

using the Kramers’ rate theory, we have calculated the fluctuating rate constant of molecular transition, as well as

the experimentally accessible quantities such as the force-dependent mean lifetime, the rupture force distribution,

and the speed-dependent mean rupture force. Particular attention is paid to the discrepancies between the kinetics

with and without dynamic disorder. Our results suggest that dynamic disorder is an important factor that should be

taken into account properly in accurate interpretations of single-molecule pulling experiments. Finally, I will talk

about the non-exponential kinetics study for DNA escape from α-hemolysin nanopores. We proposed a fluctuation

bottleneck (FB) model to investigate the non-exponential kinetics of DNA escape from nanometer-scale pores. The

basic idea is that the escape rate is proportional to the fluctuating cross-sectional area of DNA escape channel, the

radius r of which undergoes a subdiffusion dynamics subjected to fractional Gaussian noise with power-law


26

memory kernel. Such a FB model facilitates us to obtain the analytical result of the averaged survival probability

as a function of time, which can be directly compared to experimental results. Particularly, we have applied our

theory to address the escape kinetics of DNA through α-hemolysin nanopores. We find that our theoretical

framework can reproduce the experimental results very well in the whole time range with quite reasonable

estimation for the intrinsic parameters of the kinetics processes. We believe that FB model has caught some key

features regarding the long time kinetics of DNA escape through a nanopore and it might provide a sound starting

point to study much wider problems involving anomalous dynamics in confined fluctuating channels.

关键字:anomalous diffusion,dynamic disorder effect,mesoscopic statistical modeling


27

Structural modeling of proteins integrating small-angle X-ray scattering

data

张泳辉，彭俊辉，文彬，张志勇

USTC

USTC

USTC

USTC

摘要

Structure elucidation of a large biomolecule, such as a multi-domain protein or protein complex, is generally

challenging due to its high flexibility in solution. Recently, a notion of “integrative structural biology” has been

proposed, which aims to determine the protein structure and characterize its flexibility by combining

complementary high and low resolution experimental data using computer simulations. Small-angle X-ray

scattering (SAXS) is an efficient technique that can yield low resolution structural information like the size and

shape of the protein. For very flexible protein or protein complex, a screening-after-sampling strategy is often used

to elucidate the ensemble properties of these systems. In this category of approaches, a pool of structural models

starting from high resolution structures obtained by X-ray or NMR is produced, and then the structures are

screened out of the pool to best fit the SAXS data. We have investigated solution structures of several proteins,

such as the triple-BRCT-domain of epithelial cell transforming protein 2, the tandem WW domains of the forming

binding protein 21 and the tandem SH3 domains of CAP in complex with the proline rich loop of vinculin.

关键字:Integrative modeling,SAXS


28

Elucidation of Energy Transfer in the Photosystem II Reaction Center

张璐

香港科技大学

摘要

One longstanding puzzle concerning photosystem II, a core component of photosynthesis, is that only one of the

two symmetric branches in its reaction centre is active in electron transfer. To investigate the effect of the

photosystem II environment on the preferential selection of the energy transfer pathway (a prerequisite for electron

transfer), we have constructed an exciton model via extensive molecular dynamics simulations and quantum

mechanics/molecular mechanics calculations based on a recent X-ray structure. Our results suggest that it is

essential to take into account an ensemble of protein conformations to accurately compute the site energies. We

identify the cofactor CLA606 of active chain as the most probable site for the energy excitation.We further

pinpoint a number of charged protein residues that collectively lower the CLA606 site energy. Our work provides

insights into the understanding of molecular mechanisms of the core machinery of the green-plant photosynthesis.

关键字:photosystem II,MD simulations


29

蛋白质静电和氢键作用的核磁共振研究

张宁 , 李敬文 , 安辽原 , 姚礼山

中科院青岛生物能源与过程研究所




摘要

复杂的原子之间作用机制共同维持蛋白质的结构和并实现其生物功能。而实验表征测量这些相互作用通常

比较困难。最近我们发展了一种基于化学位移扰动（CSP）的核磁共振方法，定量测量了单个带电侧链氨

基酸产生的电场强度，并获得蛋白质表观介电常数。我们的结果表明盐离子、温度和拥挤环境对于电场强

度都有影响，详细的机理解析仍需要进一步的研究。在二级结构如 alpha-螺旋和 beta-折叠片中，氢键广泛

存在并形成复杂网络。我们发展了一种基于 H/D 同位素效应的核磁共振方法，来研究蛋白质氢键网络的协

同性。我们的实验结果表明，在 alpha-螺旋中，当一个氢键被扰动，周围肽平面的主链 H-N 化学位移发生

变化。结合量化计算表明，这一化学位移变化体现了这些肽平面所形成氢键的变化。即当单个氢键被削弱

时，周围若干个氢键也同时变弱，证明了 alpha-螺旋中氢键的协同性。与 alpha-螺旋相比，beta-折叠片氢键

协同性更加复杂。当一个氢键被削弱，周围氢键出现了不同响应，即某些氢键变强，而其它氢键则变弱。

关键字:静电作用,氢键协同性


30

6 月 15 日下午主会场报告

Dynamics and mechanism of ultrafast water-protein interactions

仲冬平

The Ohio State University

摘要

Abstract: Water is a universal lubricant in life and plays a critical role in biomolecular structure, dynamics and

function. Here, we report the systematic characterization of water motions around protein surfaces and their

temperature dependence. Hydration water is found to strongly slave protein fluctuations on ultrafast timescales. A

series of correlations between the dynamics and protein properties was observed. These results revealed the wide

range of heterogeneous water dynamics on the picosecond timescales but are well correlated with the protein

structures, dynamics and even function. Such water dynamics could be general at any other nano-interfaces.

关键字:Protein hydration,Coupled fluctuation


31

Integrative Metallomic Approach to Match Metal to Proteins

孙红哲 1,2, Yau-Tsz Lai1, Ligang Hu1,3, Yuen-Yan Chang1, 李洪艳 1, Yuchuan

Wang2

1Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR; 2School of

Chemistry and Chemical Engineering, Sun Yat-sen University, P.R. China ; 3Research Center for

Eco-Environmental Sciences, the Chinese Academy of Sciences, 100085, P.R. China (E-mail: [email protected])

摘要

Metal ions operate as cofactors for around 40% enzymes, however, they also exhibit toxic effects. It is crucial to

identify metal-protein interactions at a proteome-wide scale (1) which are difficult due to some weak and transient

interactions. We developed an integrated approach consisting of gel electrophoresis and inductively coupled

plasma mass spectrometry, LA-ICP-MS, IMAC, fluorescence and bioinformatic approach to identify

metal-associated proteins using bismuth antiulcer drug and silver as an example (2,3). We developed a

comprehensive and robust strategy to readily identify metal-associated proteins as well as to quantify the metals

for fast metallome/proteome-wide profiling of metal-binding proteins. Metal-tunable fluorescence probe can track

both His-tagged proteins and metal-binding proteins in live cells (4). The probe could also be used in

metalloproteomics (5). We also established a bioinformatic method which allows potential metal-binding proteins

both sequentially and spaciously to be searched (6,7). We show that histidine-rich proteins (HRPs) are extensively

distributed in prokaryotic proteomes, with the majority of HRPs being involved in metal homeostasis. Importantly,

the occurrence of histidine-rich proteins in the proteomes of prokaryotes is related to their habitats.

This work was supported by the RGC of Hong Kong (7039/13P, 173046/14P) and HKU (for an e-SRT on

Integrative Biology).

References:

[1] H. Sun (ed.) Biological Chemistry of Arsenic, Antimony and Bismuth 2011, John Wiley & Sons, Chiester.

[2] C.N. Tsang, J. Bianga, H. Sun, J. Szpunar, R. Lobinski, Metallomics 2012, 4, 277.

[3] L.G. Hu, T.F. Cheng, G.B. Jiang, H. Sun etc, Angew Chem Int Ed 2013, 52, 4916.

[4] Y.T. Lai, Y.Y. Chang, L. Hu, Y. Yang, A. Chao, H. Sun etc , Proc Natl Acad Sci USA, 2015, 112, 2948.

[5] Y.F. Hong Y, Y.T. Lai, CF Chan, H. Sun (2015) Proc Natl Acad Sci USA 2015, 112, 3211.

[6] T. Cheng, W. Xia, P. Wang, F. Huang, J. Wang, H. Sun, Metallomics 2013, 5, 1423.

[7] Y. Wang, C.N. Tsang, F. Xu, P.W. Kong, L. Hu, J. Wang, I.K. Chu, H. Li, ,H Sun Chem Commun 2015, 51,

16479.


32

6 月 15 日下午分会场报告 a（15:40-17:20）

Functional Photoactive Protein Synthesis Using Genetic Code Expansion

王江云

Institute of Biophysics, Chinese Academy of Sciences 15 Datun Road, Chaoyang District, Beijing 100101

E-mail: [email protected]

摘要

The ability to selectively modify proteins with fluorescent probes has greatly facilitated both in vitro and in vivo

studies of protein structure and function. Here we report that genetic code expansion can significantly improve our

ability to visualize the proteome.

We are the first to report the genetic incorporation of a fluorescent amino acid (CouAA) into proteins in E. coli

in response to the amber stop codon. Recently, we have successfully incorporated unnatural amino acids bearing

cyclopropene or tetrazole functional groups. Through photoclick reaction, we can site-specifically attach any

biophysical probe to a specific site of a target protein in vivo. The photoclick reaction has the following

advantages: its fast rate (50 M-1s-1) allows for efficient protein labeling in one minute; spatiotemporal control by

laser. We are now applying this technology for super-resolution imaging, post-translational modification sensing,

as well as imaging in living plants. We have significantly expanded the function of fluorescent proteins through

the genetic incorporation of metal-chelating unnatural amino acids. In recent works, we have bestowed GFP with

metal-sensing function, and emission spectra in the infrared range. We are now using these new GFP variant for

deep-tissue imaging. Most recently, we have designed an acid and Mn(III) turn-on fluorescent protein sensor based

on genetic code expansion. We are currently using this method for protein and virus endocytosis. These

unpublished works will be discussed in the conference.

关键字：Genetic Code Expansion, photoclick

References:

Liu,X. H.; Li, J. S.; Dong, J. S.; Hu,C.; Gong, W. M. Wang, J. Y. Angew. Chem. Intl. Ed. 2012, 51, 10261-10265.

Yu, Z.; Y. Pan, C.; Wang, Z. Y.; Wang, J. Y.; Lin, Q. Angew. Chem. Intl. Ed. 2012, 51, 10600-10604.

Wang, J. Y.; Zhang,W.; Song,W. J.; Wang,Y. Z.; Yu, Z. P.; Li, J. S.; Wu, M. H.; Wang, L.; Zang, J. Y.; Lin, Q. J.

Am. Chem. Soc. 2010, 132, 14812-14818.

Liu, X. H.; Li,J. S.; Hu,C.; Zhang,W.; Hu, M. R.; Zhou,J.; Wang, J. Y. Angew. Chem. Intl. Ed. 2013, 52,

4805-4809.

Li, F. H. Zhang, H.; Sun, Y.; Pan, Y. C.; Zhou, J. Z.; Wang, J. Y. Angew. Chem. Intl. Ed. 2013, 52, 9700-9704

Liu,X. H.; Jiang, L.; Li, J. S.; Wang, L.; Yu,Y.; Zhou, Q.; Lv, X. X.; Gong,W. M.; Lu,Y.; Wang, J. Y. J. Am.

Chem. Soc., 2014, 136, 13094–13097.


33

Synthesis, characterization and biological activities of a Valen Schiff base

and its bismuth(III) complex

李旭，李传华，蒋建宏，肖圣雄，李霞，张辉，李强国

Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Applications, College of

Chemistry Biology and Environmental Engineering, Xiangnan University,






Chemistry Biology and Environmental Engineering, Xiangnan University







摘要

Abstract In this work, a new Schiff base ligand

[N,N'-bis(2-hydroxy-3-methoxyphenylmethylidene)-2,6-pyridinediamine, C21H19N3O4] (abbreviated as H2L, L=

C21H17N3O4) and its bismuth(III) complex, [Bi(C21H17N3O4)]Cl2H2O (abbreviated as [Bi(L)]Cl×2H2O) were

synthesized in ethanol and THF solvent, respectively. The compositions and structures of two synthetic

compounds were characterized by spectrometry (NMR, MS, UV-visible and FT-IR), elemental analysis, chemical

analysis, molar conductivity, thermogravimetric analysis and X-ray powder diffraction. The inhibitory activities of

the ligand and its bismuth(III) complex on the growth of Helicobacter pylori (abbreviated as H. pylori) and

Schizosaccharomyces pombe (abbreviated as S. pombe) were studied by microcalorimetry, respectively. The

experimental results indicated that the ligand stimulated the growth of H. pylori, while the complex inhibited its

growth. By contrast, both the ligand and the complex inhibited the growth of S. pombe, but the inhibitory effect of

the complex was stronger than the ligand. In addition, the interaction of the complex and bovine serum albumin

(BSA) was investigated by fluorescence spectroscopy. The results revealed that the formation of the complex-BSA

led to the fluorescence quenching of BSA. Moreover, The synchronous fluorescence spectra showed the

interaction between the complex and BSA could change the microenvironment and conformation of BSA.

关键字:Microcalorimetry,Schiff base,Bismuth(III) complex,H. pylori,S. pombe,Bovine serum albumin

http://xueshu.baidu.com/usercenter/data/author?cmd=authoruri&wd=authoruri%3A%289f64c342930c84d1%29%20author%3A%28%E6%9D%8E%E6%97%AD%29%20%E6%B9%98%E5%8D%97%E5%AD%A6%E9%99%A2%E5%8C%96%E5%AD%A6%E4%B8%8E%E7%94%9F%E5%91%BD%E7%A7%91%E5%AD%A6%E7%B3%BB

http://xueshu.baidu.com/s?wd=authoruri%3A%28cd9208ee93a088c3%29%20author%3A%28%E5%BC%A0%E8%BE%89%29%20%E6%B9%98%E5%8D%97%E5%AD%A6%E9%99%A2%E5%8C%96%E5%AD%A6%E4%B8%8E%E7%94%9F%E5%91%BD%E7%A7%91%E5%AD%A6%E7%B3%BB&tn=SE_baiduxueshu_c1gjeupa&ie=utf-8&sc_f_para=sc_hilight%3Dperson&sort=sc_cited


34

Position-dependent effects of ribose G-quartets in intramolecular

G-quadruplex

周俊

南京大学

摘要

To resolve the exact role of ribose G-quartets and how they affect the properties of G-quadruplex structures, we

designed a parallel DNA intramolecular G-quadruplex, in which we selectively substituted DNA G-quartets by one,

two, or three RNA quartets. Biophysical characterization demonstrate that these RNA-DNA chimeras all form

parallel monomorphic G-quadruplex structures. Thermal stability results show that ribose G-quartets have

position-dependent and cumulative effects on the G-quadruplex. An unexpected destabilization effect was

observed when ribose G-quartets were present in the 5'-G-quartet. This observation challenges the general belief

that RNA residues stabilize G-quadruplexes. Furthermore, hydration effects are not the sole factor determining the

stability of RNA G-quadruplexes, and molecular modeling results reveal that hydrogen bonds are also crucial for

the stability of RNA G-quadruplexes. These analyses highlight the role of ribose G-quartets on G-quadruplexes,

and demonstrate that their positions are critical for the properties of RNA G-quadruplexes.

关键字:G-quadruplex,ribose G-quartet


35

Toll 样蛋白受体 13 的天然免疫识别和调控

王晓辉

中国科学院长春应用化学研究所化学生物学实验室

摘要

天然免疫系统是机体保护病原菌感染的进化保守机制，Toll 样蛋白受体（Toll-like receptors，TLRs）是天然

免疫模式识别受体，识别外源的病原菌分子相关模式和内源的损害分子相关模式，诱导炎症免疫反应。

TLR13 受体特异性识别细菌 23S 核糖体 RNA，是 TLR 家族被忽视的受体，其信号通路的天然免疫分子识

别和调控的化学过程中许多基础科学问题不清楚。研究发现 TLR13 ssRNA 配体的发卡结构是其被 TLR13

特异性识别的结构基础。损害分子相关模式高迁移率族蛋白 B1（high mobility group box B-1, HMGB1）也

能高亲和力识别 TLR13 ssRNA 配体，HMGB1 结合导致 TLR13 配体的发卡结构破坏，其负调控 TLR13 信

号通路，并且 HMGB1 的氧化还原态对其识别和调控 TLR13 信号通路非常重要。

关键字:Toll 样蛋白受体,分子识别


36

6 月 15 日下午分会场报告 b（15:40-17:20）

线粒体靶向药物

刘义 , 樊晓阳 , 何欢 , 蒋风雷

武汉大学化学与分子科学学院




摘要

线粒体是细胞代谢过程扮演重要角色的奇妙细胞器，同时也是一个半自主性细胞器。近年来的研究发现：

线粒体是许多药物和毒物作用的靶细胞器，线粒体重新成为研究热点。有科学家用“mitochondria make come

back”来概括这种现象。以线粒体为靶点的药物，是抗肿瘤药物的新发展方向。探究以线粒体为靶点的药物

对线粒体功能影响，可以更好的理解药物对线粒体的作用机制，为药物分子设计提供重要参考。线粒体靶

向抗肿瘤药物，能诱导线粒体发生基质肿胀、膜电势下降、膜渗透转换等过程。说明它们的抗肿瘤效果可

能与通过线粒体途径诱导肿瘤细胞凋亡有关。我们设计、合成了系列线粒体靶向药物，包括有机胂抗肿瘤

化合物，发现有机胂具有比无机砷更优异的抗肿瘤活性，且可靶向到线粒体，能够显著提高化合物的选择

性。将 F16 与 BODIPY 通过共轭共价连接，构建多功能分子，在一个分子中成功实现了荧光示踪、线粒体

靶向、抗肿瘤等三大功能，实现”Lab-on-a- molecule”的设计理念，该分子对肿瘤细胞具有高活性和高选择

性。

关键字:线粒体,靶向药物,基质肿胀,膜电势,作用机制


37

仿生纳米马达的构建及应用

玄明君 , 戴陆如 , 贺强 , 李峻柏

中国科学院化学研究所

国家纳米科学中心

哈尔滨工业大学


摘要

仿生自驱动纳米马达作为一种人工合成器件，依靠其特殊结构，仿造生物分子马达能量转化的功能，将不

同形式的能量用于机械运动。目前，人工合成纳米马达主要借助催化分解过氧化氢产生氧气泡，产生反冲

力实现驱动。为了降低有毒化学“燃料”的使用，实现纳米马达在生物相关领域的潜在应用研究，国内外学

者又发展了自电泳、表面张力、离子浓度梯度、磁场、超声波等驱动机理。我们的研究兴趣集中在各种仿

生自驱动纳米马达的制备、驱动机制的研究，及在生物医学等领域的应用探索。如图 1 所示，我们通过溶

胶凝胶法和化学气相沉积法制备了一系列带有 Janus 结构的自驱动纳米马达，先后实现气泡驱动、近红外

光驱动，以及作为药物载体用于抗肿瘤的研究。特别是近红外光驱动的纳米马达可完全克服对化学“燃料”

的依赖，极大的增强仿生自驱动纳米马达在生物相关领域的应用前景。

关键字:仿生,纳米马达,化学驱动,光驱动,运输载体


38

仿生多尺度孔道的研究

侯旭

厦门大学

摘要

生物物理化学是物理化学的一个相对新的分支，这一学科研究的共同特征是运用物理化学的思想、方法和

工具探究生物体系，为生命科学研究提供新的方法和技术，用化学的眼光寻求生命现象的解释。自然界的

生物体经过亿万年的进化几乎完成了智能操纵的所有过程，学习生物中物理化学现象和性质将为我们带来

取之不尽的智能新材料和新体系的设计研发灵感。当前，生物物理化学家十分关注生物材料和仿生材料的

发明、创造，以及这些材料的物理化学性质。仿生孔道因其在物质分离、流体器件等领域具有广阔的应用

前景，近年来在国内外引起了广泛关注。深入观察和研究生物多尺度系统的结构、功能以及物化性质，是

设计开发仿生孔道的关键因素。受生物体中孔道的启发，在多尺度孔道系统中，引入仿生液体门控机制，

设计开发新型功能孔道，把传统的固体/气体和固体/液体体系的科学问题转移到了固体液体/气体和固体液

体/液体体系。以多尺度系统地研究微/纳尺度孔道和门控液体化学组成对输运流体和门控性能的影响,将推

动仿生孔道在生物医学、智能薄膜、物质分离、污水处理领域的实际应用。

关键字:仿生孔道,多尺度


39

从原子的相互作用到细胞的恶性转变：多尺度方法研究慢性炎症-癌

症相互关系的分子机制

廖结楼



40

6 月 15 日下午分会场报告 c（15:40-17:20）

The Sequence Preference in DNA Methylation Level and Its Structural Basis

in Mammalian

高毅勤 , 张玲 , 古婵

北京大学

北京大学

北京大学

摘要

Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic

modifications in mammalian DNA. The methylation level distribution is bimodal. Here, we develop an algorithm

to quantify the bimodal methylation level distribution and find that in the tetranucleotides 5’-NCGB-3’ (N=A, C,

G or T and B=A, C, G or T), GCGB and CCGB show more apparent bimodalities than ACGB and TCGB. Such a

finding indicates that GCGB and CCGB are less variant in the level of methylation. The degrees of bimodalities of

NCGB are conserved among different cells, tissues and species, indicating common features in the mechanisms of

methylation and demethylation, presumably mediated by DNMTs and TETs in mammalians, respectively. Using

MD simulations, we find that the DNA intrinsic structure properties of CpG/5mCpG sites are indeed significantly

affected by the flanking sequences N and B, in NXGB (X=C or 5mC). In accordance with the sequencing data

analysis, compared with GXGB and CXGB, AXGB and TXGB adopt conformations biased toward base flipping,

thus are proposed to be more active for methylation and demethylation.

关键字:DNA methylation,biomodal distribution


41

红外光谱的检测灵敏度和选择性研究进展及其在生物体系中的应用

张文凯 , MarkiewiczBeatrice , RodgersJeffrey , 陈建新 , 盖锋

北京师范大学





摘要

红外光谱已被广泛应用于各种多肽和蛋白质的结构和动力学的研究中。但在推广到生物大分子体系的研究

时却面临着很多困难，主要原因是目前红外光谱的选择性不够好和灵敏度不够高。因此，在多数情况下人

们无法通过生物分子自带的振动模式来获得位点选择的蛋白质结构和动力学信息。为了解决这些困难，我

们发展了非天然氨基酸红外光谱探针并把它们结合到蛋白质中去进行位点选择的光谱研究，我们也发展了

提高二维红外光谱检测灵敏度的实验方法。在此基础上，我们对一些蛋白质体系展开了研究工作。例如，

我们研究了甲型流感病毒中的离子通道 M2，它是由低 pH 激活的质子选择性离子通道，它的质子传导是甲

型流感病毒复制的关键步骤，同时也是抗病毒药物的主要目标对象。过去的研究认为甲型流感病毒 M2 离

子通道内的质子传导的调控是依赖于通道中的水的结构变化。前人的研究表明通道中的 Trp41 氨基酸残基

是负责通道开启和关闭的阀门，我们利用 TrpCN 红外探针研究了不同 pH 值情况下通道中的水的结构和动

力学变化。研究结果表明，Trp41 氨基酸残基附近的水的结构在通道开启和关闭的情况下没有显著的变化。

关键字:红外光谱探针,二维红外光谱,离子通道


42

Ultrafast Dynamics in DNA Model System with Diverse Structures

陈缙泉

华东师范大学

摘要

Ultrafast laser experiments on carefully selected DNA model compounds probe the effects of base structure, base

stacking, base pairing, and structural disorder on excited electronic states formed by UV absorption in single

nucleic base as well as single and double DNA strands. Direct π-orbital overlap between two stacked bases in a

dinucleotide or in a longer single strand creates new excited states that decay orders of magnitude more slowly

than the generally subpicosecond excited states of on omeric bases. Half or more of all excited states in single

strands decay in this manner. Ultrafast mid-IR transient absorption experiments reveal that the long-lived excited

states in a number of model compounds are charge transfer states formed by interbase electron transfer, which

subsequently decay by charge recombination. The lifetimes of the charge transfer states are surprisingly

independent of how the stacked bases are oriented, but disruption of π-stacking, either by elevating temperature or

by adding a denaturing co-solvent, completely eliminates this decay channel. In double strands, hydrogen bonding

between bases perturbs, but does not quench, the long-lived excited states. Kinetic isotope effects on the

excited-state dynamics suggest that intrastrand electron transfer may couple to interstrand proton transfer. By

revealing how structure and non-covalent interactions affect excited-state dynamics, on-going experimental and

theoretical studies of excited states in DNA strands can advance understanding of fundamental photophysics in

other nanoscale systems.

关键字:DNA photophysics,Excited-state dynamics,Femtosecond transient absorption


43

Ion Effect on Hydrogen Bonding Network in Water

庄巍

中国科学院福建物质结构研究所

摘要

Ions effect on water structure and dynamics have significant specificity which is far from being fully

comprehended. Various vibrational spectroscopies are among the most powerful experimental tools to explore this

issue. The interpretation of these spectroscopy signals is, however, usually non-trivial and requires the help from

theoretical studies. We've developed a series of theoretical approaches to simulate the analyze the vibrational

spectroscopies of the ionic solution, which reproduce nicely the spectra including THZ, Raman, fsIR,2DIR,IRPD

and Raman-THZ. Based on these simulations, we attempt to address several important issues about the ion effect

on water hydrogen bonding network, including 1) ion specificity in their effects on water dynamics and 2) spatial

range of ion effects. Novel techniques including complex network recognition and gaussian field model are

employed to assist the analysis.

关键字:vibrational spectroscopies,Ions effect


44

6 月 15 日晚上研究生报告专场 1（20:00-21:40）

A single-molecule study of diffusion of AlkD on dsDNA by FRET-FCS

潘白龙 , 赵新生

北京大学

北京大学

摘要

N3-methyladenine(3mA) and N7-methylguanine (7mG) are reported as high toxic damages on double-stranded

DNA (dsDNA). AlkD protein discovered in Bacillus cereus has glycosylase acivity to remove N3- and

N7-alkylpurines. Interestingly, unlike other glycosylases which use a plug to recognize damages, AlkD seems to

detect the damaged base pair by interaction with the backbone of dsDNA[1]. The dynamic mechanism for its

lesion detection remains unresoved. We conducted single-molecule experiments with substrate DNA immobilized

on surface by a scanning confocal microscope and found the diffusion process of AlkD on dsDNA by FRET-FCS.

The diffusion rate is dependent on GC contents and different mutations, which may reveal the mechanism of lesion

searching.

关键字:single-molecule,AlkD,diffusion,FRET-FCS


45

铜锌超氧化物歧化酶与 DNA 相互作用的热力学研究

李享 , 刘长林 , 王珊珊

华中师范大学化学学院



摘要

十年前我们在溶液中发现铜锌超氧化物歧化酶(SOD1)能与 DNA 结合时，推测胞内该酶应该是一种 DNA 结

合蛋白。SOD1 的经典功能是催化超氧阴离子歧化，维持胞内 ROS 内稳态和信号网络正常。Tsang 等人发

现 SOD1 调控 100 多个基因的表达，提出该酶是一种核转录因子。SOD1 可能作为一种感应胞内 ROS 水平

的金属转录因子，所以研究生理条件下 SOD1 与 DNA 的结合具有重要的生物学意义。通过小角 X-射线散

射，研究了溶液中 SOD1 与 DNA 相互模式，SOD1 的无规卷曲区域与 DNA 的大沟结合。对 SOD1-DNA 相

互作用进行模拟计算，发现 SOD1 与双链 DNA 的结合可能以横向顺式和纵向沟槽结合，与 SAXS 类似 DNA

接触的区域主要分布在 SOD1 活性部位附近处的无规卷曲区。参考分子对接的模型以及与 SOD1 结构类似

的 p53 与 DNA 的相互作用模式，设计了回文 DNA，进一步证明了 DNA 与 SOD1 的相互作用。我们在溶

液中发现野生型 SOD1 及其突变体 A4V 与 DNA 结合，在中性 pH，二者结合的平衡常数 Kb > 104 M-1；降

低溶液 pH，Kb 至少上升一个数量级；氧化的野生型 SOD1，Kb > 107 M-1；突变体 A4V 与 DNA 的结合比

野生型 SOD1 更加紧密。同时，DNA 作为模板促进 SOD1 的聚集这一现象对于理解 SOD1 寡聚体的致病机

理以及相关疾病(如 ALS)治疗也具有重要意义。

关键字:铜锌超氧化物歧化酶,DNA,SOD1-DNA 复合物


46

分子动力学模拟研究 ANCA 探针与 Aβ 纤维结合模式

何欢，蒋风雷，刘义

Wuhan University

Wuhan University

Wuhan University

摘要

多肽和蛋白质的错误折叠形成不溶性的淀粉样纤维，是类淀粉疾病的重要标志。临床研究当中对淀粉样纤

维的检测主要依赖于能与淀粉样纤维特异性结合的探针。ANCA 分子是一种近红外发光的蛋白纤维检测探

针，研究表明 ANCA 分子与不同种类的蛋白纤维结合后，其荧光发射波长不同，具有体内识别不同蛋白纤

维的潜力。ANCA 分子具有良好的应用前景，但其与蛋白纤维结合模式的研究受到蛋白纤维的不溶性和不

可结晶性的阻碍。我们通过分子动力学模拟的方法，研究了 ANCA 分子与 Aβ40 蛋白纤维(PDB : 2lmn)的结

合模式。研究发现，ANCA 分子在 Aβ40 蛋白纤维上的结合位点主要有两个：位点 I 由 K16、V18 和 F20

的侧链以及 L17 和 F19 的主链形成的结合口袋，ANCA 分子与 Aβ 纤维主轴的方向平行；位点 II 由 Y10 以

及 V12 的侧链形成的结合口袋，在这种结合模式当中，ANCA 分子与 Aβ 纤维主轴的方向垂直。在结合位

点 II 当中，两个 ANCA 分子会由于萘环的 π-π 堆积作用形成二聚体。在这两个结合位点当中，ANCA 分子

与蛋白纤维之间主要作用力均为范德华力，但是其与带正电的氨基酸(H13 和 H14)之间的静电作用力对二者

的结合也起到关键作用。采用 MM-GBSA 方法，计算 ANCA 分子在两个位点的结合自由能分别为-26.55

kcal/mol 和-46.58 kcal/mol。

关键字:淀粉样纤维,Aβ40,ANCA 探针


47

Kinetics study reveals the mechanism of the interaction between Cu(II) and

Amyloid-β peptides

李皓然 , 葛保胜 , 黄方

中国石油大学（华东）



摘要

It is believed that metal ions play crucial roles in the aggregation of amyloid-β (Aβ) peptides, which is supported

by fact that some metal ions can induce irreversible aggregation of peptides or greatly accelerate the aggregation

process[1]. It is highly demanded to reveal the mechanism of the interaction between Aβ and metal ions to regulate

or prevent the interaction. Utilizing the fluorescence quenching of an extrinsic probe by Cu(II)[2], we have studied

the binding kinetics between Cu(II) and Aβ peptides under physiologically relevant conditions, including the wild

type and peptides corresponding to English(H6R), Tottori(D7N) familial mutations. The comparison of the binding

kinetics between Cu(II) and different mutants allow us to propose a model describing the binding process. The

establishment of the interaction mechanism will help to develop new measures regulating the binding process and

amyloid formation.

关键字:Amyloid beta,Copper, Kinetics,Fluorescence spectroscopy,Reaction mechanism


48

Uncovering amyloid formation mechanism of yeast prion Ure2 by single

molecule FRET and kinetic analysis

杨洁， DearAlexander , KnowlesTuomas P.J. ，吴思， PerrettSarah

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

Department of Chemistry, University of Cambridge

Department of Chemistry, University of Cambridge



摘要

Protein aggregation to form amyloid fibrils is associated with a variety of neurodegenerative diseases, in which

oligomeric intermediates formed during the early stages cause neurotoxicity to cells. Due to the low-populated,

metastable and heterogeneous nature of oligomers, it is hard to determine the conformation details and

microscopic reactions during oligomeric assembly. Single molecule fluorescence spectroscopy makes it possible to

probe prefibrillar oligomers and reveal the dynamics of amyloid assembly. Here, we applied single molecule

fluorescence resonance energy transfer (smFRET) to investigate the oligomers formed during the amyloid

formation of the yeast prion protein Ure2, which is the protein determinant of the Saccharomyces cerevisiae prion

state [URE3]. In this study, oligomerization of Ure2 during the lag phase is clearly observed by single molecule

FRET measurements and two types of Ure2 oligomers with different assembly conformations were directly

identified, where the late oligomer has a compact structure, suggesting an on-pathway oligomerization process.

Moreover, by analysis of the aggregation kinetics of two Ure2 mutants using combined single molecule and

ensemble kinetic data, we obtained the parameters that describe the microscopic reaction steps of amyloid

assembly. The difference between the rate constant of oligomerization and amyloid nucleation indicates a two-step

mechanism for Ure2 fibrillization, in which the initially formed oligomers undergo conformational conversion to

β-sheet rich oligomers as extendable amyloid nuclei. These results shed light on the microscopic mechanism of

amyloid formation and have implications for anti-degenerative therapeutic strategies targeted to oligomeric

intermediates.

关键字:Ure2,amyloid formation,oligomeric intermediate,single molecule FRET


49

6 月 15 日晚上研究生报告专场 2（20:00-21:40）

飞秒时间分辨和频光谱系统的发展与应用

谈军军


摘要

生物膜上的蛋白质分子作为生命体行使特定生理功能的分子机器，在细胞活动和生命过程中扮演着非常重

要的角色。其在行使特定生理功能时，往往包含氢键等分子间作用的断裂和重新形成，光合作用、能量代

谢等重要生命过程中的能量与电子转移等过程。从分子水平上深入研究蛋白质能量与电子转移等过程是揭

示生物大分子重要生理功能物理化学机制的关键,对超快时间尺度内的界面表征技术提出了重要需求。最近,

我们发展了飞秒宽带和频光谱探测技术。以蛋白质跨膜过程为模型，研究了蛋白质在跨膜过程中的结构变

化，获得了跨膜这一不可逆过程毫秒时间分辨的分子结构变化，观察到蛋白质从 loop 结构到螺旋结构转变

过程中 N-H 振动的相位反转过程。在此基础上，我们发展了飞秒时间分辨和频光谱探测技术。通过振动态

选择激发生物膜蛋白质 N-H 基团，然后利用飞秒宽带红外和频光谱系统探测其动态振动能量转移过程，获

得了生物膜上多肽分子在不同氢键环境下的能量传递信息。

关键字:界面蛋白质,界面能量转移,飞秒时间分辨,和频光谱


50

羧基取代偶氮苯类双亲分子的表面结构与组装特性研究

夏文秀，胡中进，魏锋，ZhuXue Feng，郑万泉

江汉大学

江汉大学

江汉大学

中国科学院新疆理化技术研究所

巴黎第十一大学分子科学研究所

摘要

偶氮苯类分子被广泛地用于构建不同的界面材料与生物传感器。偶氮苯类双亲分子的表面分子结构与组装

特性的不同对传感器的性能影响较大，因此本实验利用 LB 膜分析仪、紫外可见吸收光谱仪、和频振动光

谱分析仪对不同的偶氮苯双亲分子（在 2,3,4 位上分别用羧基取代）在界面上的分子结构及其组装特性，以

及其结构随 pH 值的变化进行研究。本实验通过运用 LB 膜分析仪压膜法，获得不同偶氮苯分子在不同 pH

值下的膜压曲线，用于分析偶氮苯分子单层膜的组装特性；通过 LB 膜分析仪提拉法，获得偶氮苯的单层

膜与多层膜，从而形成传感器模型体系；利用紫外可见吸收光谱仪得到紫外可见吸收光谱图，可以获得偶

氮苯分子转移到固体基底的组装特性；最后用和频振动光谱分析仪（Sum frequency generation vibrational

spectroscopy：SFG-VS）来表征偶氮苯双亲分子结构与取向角度。实验数据表明，在 pH=7 的情况下，2 位

羧基取代的偶氮苯分子（2AC）在界面上容易形成 J-aggregate，3 位羧基取代的偶氮苯分子(3AC)及 4 位羧

基取代的偶氮苯分子(4AC)容易形成 H-aggregate；在 pH=9 的情况下，由于是碱性环境，失去质子，使得共

轭结构发生变化，导致 2AC、3AC 及 4AC 均形成 H-aggregate。

关键字: LB 膜分析仪,和频振动光谱分析仪（SFG-VS）


51

于石墨烯量子点的功能性纳米荧光探针的构建以及在生物技术中的

应用

王雅楠 , 隋媛红 , 王晓娟 , 黄方

中国石油大学（华东）生物工程与技术中心




摘要

基于石墨烯量子点的功能性纳米荧光探针的构建以及在生物技术中的应用王雅楠，隋媛红，王晓娟*，黄方

* 中国石油大学（华东）重质油国家重点实验室，266580，青岛石墨烯量子点是纳米材料中一个新成员，

它保留了石墨烯的单原子层和蜂窝状的平面结构，同时它的极小尺寸（直径 40 纳米以下）和边缘效应赋予

了它稳定的荧光特性和良好的水相分散性。我们对石墨烯量子点在生物技术方向的应用进行了有效的探索

和开拓。利用石墨烯量子点边缘带有大量羧基，易于修饰的特点，我们将具有肿瘤靶向性的叶酸配体分子

通过化学键和石墨烯量子点连接，同时利用石墨烯量子点比表面积大，具有大量苯环结构的特点，将抗癌

药物阿霉素负载到石墨烯量子点表面，构建了多功能纳米探针 1,2。该材料同时实现了肿瘤细胞选择性标记、

靶向药物输送、以及实时追踪药物载体和药物运动过程的多重功能。此外，石墨烯量子点具有良好的光热

性能，利用这一性能，我们将ＤＮＡ适配体修饰到石墨烯量子点表面，构建了两组分肿瘤诊断治疗试剂 3，

为癌症的诊断和治疗提供了新思路。我们还利用氨基小分子对石墨烯量子点进行改性，构建了特异性地标

记细胞核仁的新型纳米荧光探针，为研究核仁这一重要细胞器的结构和功能提供了有效的检测手段 4。参

考文献 (1) Wang, X.; Sun, X.; Lao, J.; He, H.; Cheng, T.; Wang, M.; Wang, S.; Huang, F. Colloids Surf B

Biointerfaces2014, 122, 638. (2) He, H.; Wang, X.; Feng, Z.; Cheng, T.; Sun, X.; Sun, Y.; Xia, Y.; Wang, S.;

Wang, J.; Zhang, X. J. Mater. Chem. B2015, 3, 4786. (3) Wang, X.; Sun, X.; He, H.; Yang, H.; Lao, J.; Song, Y.;

Xia, Y.; Xu, H.; Zhang, X.; Huang, F. J. Mater. Chem. B2015, 3, 3583. (4) Wang, X.; Wang, Y.; He, H.; Chen, X.;

Sun, X.; Sun, Y.; Zhou, G.; Xu, H.; Huang, F. J. Mater. Chem. B2016, 4, 779.

关键字:石墨烯量子点,药物输送,共聚焦显微成像


52

基于荧光乙二醇壳聚糖衍生物的脂筏原位成像

蒋耀文 , 郭皓月 , 吴富根

东南大学

东南大学

东南大学

摘要

细胞膜中富含鞘磷脂、胆固醇以及部分膜蛋白的脂筏区域对于细胞的诸多功能，如物质运输、细胞信号传

导以及膜的流动性等具有关键的作用，因此对其结构与功能的深入了解十分重要。在对脂筏的成像研究中，

光学示踪的手段与其他技术如核磁共振、质谱以及原子力显微镜等相比具有快速、原位和非侵入性等优势。

然而目前常规的荧光探针通常都受限于生物相容性差、抗干扰性弱等缺点而无法拓展其应用。与此同时，

近来生物降解型高分子在生物医学方面的应用及发展颇为引人关注。乙二醇壳聚糖作为一种壳聚糖的衍生

物，具有良好的生物相容性，在各 pH 值的水溶液中都可以溶解，而且由于其特殊的结构而便于进行各类

修饰。本文中采用共价接枝有异硫氰酸荧光素的乙二醇壳聚糖成功实现了对模型膜（支撑磷脂双分子层以

及巨型囊泡）以及真实细胞中脂筏区域的原位可视化。荧光乙二醇壳聚糖分子与脂筏区域之间可以通过静

电作用以及疏水作用而实现对脂筏区域的特异性染色。由于不需要完全插入磷脂双分子层中，荧光乙二醇

壳聚糖不会对脂筏区域的有序性造成扰动，相比于其他荧光探针，如需要与磷脂预混或对膜有扰动的探针

分子，该高分子型荧光探针具有更精确和更方便的原位成像效果。此外，我们发现该探针分子能对活细胞

的脂筏区域实现较长时间（不内吞）的成像。这一工作提供了一种新的脂筏成像手段并将加深人们对生物

大分子与磷脂膜的相互作用的认识。

关键字:脂筏,原位成像,荧光,乙二醇壳聚糖


53

基于 DNA 和金属离子特异性作用的多输入分子逻辑门

李菁菁

同济大学化学系

摘要

基于 K+/Ag+/Hg2+与一条富 GT 碱基的 DNA 的特异性相互作用，以 G-四链体特异性识别染料 NMM 为输

出信号，构建了一种三输入的 OR-INHIBIT 复合型逻辑门。钾离子会将单链 DNA 诱导成 G-四链体结构，

银离子会与 DNA 上的 G 碱基螯合，汞离子不仅会与 DNA 上的 T 碱基结合，形成 T-Hg2+-T 的结构，而且

能与 NMM 作用。因此，该逻辑门可用于 DNA 和金属离子的检测。

关键字:DNA,金属离子,分子逻辑门


54

6 月 15 日晚上研究生报告专场 3（20:00-21:40）

Motions of Allosteric and Orthosteric Ligand Binding Sites in Proteins are

Highly Correlated

马晓旻，孟虎，来鲁华

Peking University

Peking University

Peking University

摘要

Allostery, in which the binding of a ligand at one site of a macromolecule can affect other distant sites in the same

macromolecule, plays a key role in many biological processes. Theoretically, all non-fabric proteins are potentially

allosteric. However, known allosteric proteins are few in number and the identification of novel allosteric sites

remains a challenge. Because the motion of residues and subunits underlies protein function, we hypothesized that

the motions of allosteric and orthosteric sites are correlated. Using a dataset of 24 known allosteric sites from 23

monomer proteins, we calculated the correlations between potential ligand binding sites and corresponding

orthosteric sites using an approach based on the Gaussian Network Model (GNM). Most of the known allosteric

sites showed high correlations with corresponding orthosteric sites, while other surface cavities did not. These high

correlations were robust when different structural data for the same protein were used, such as structures for the

apo state and the orthosteric effector-binding state. And the contributions of different frequency modes to motion

correlations depend on proteins. The correlations were also observed in oligomeric allosteric proteins. We applied

motion correlation analysis to predict additional potential allosteric sites in the 23 monomer proteins, and some of

the predictions were in good agreement with published experimental data. We also performed motion correlation

analysis for 15-lipoxygenase, an enzyme in the arachidonic acid metabolic network, with recently reported

activating compounds in a novel allosteric site. Our analysis correctly identified this an allosteric site, along with

two other sites that are currently under experimental investigation. Our study demonstrates that allosteric sites are

highly correlated in motion with orthosteric sites, and that this type of correlation analysis provides a new way to

predict potential allosteric sites.

关键字:Gaussian Network Model,correlation,allosteric site prediction,cavity


55

Tertiary Structure Formation in Simian Retrovirus Type 1 RNA Pseudoknot

Increases Mechanical Stability and −1 Ribosomal Frameshifting Efficiency

钟振声, 杨丽霞 , 陈刚

Nanyang Technological University



摘要

Many RNA viruses including Simian Retrovirus type 1 (SRV-1) utilize minus-one ribosomal frameshifting as an

alternative translation mechanism to generate stable ratios of structural and catalytic proteins. The detailed

mechanism of minus-one ribosomal frameshifting is still not well understood. The SRV-1 frameshifting

pseudoknot is located in the overlapping region of gag and pol genes and plays critical roles in stimulating

frameshifting. We applied single-molecule force spectroscopy and steered molecular dynamics simulation to probe

the mechanical stability of the wildtype SRV-1 frameshifting RNA pseudoknot and its mutants. In addition, we

carried out ensemble thermal denaturation and native polyacrylamide gel electrophoresis studies. Our studies

reveal that the minor-groove base triple formation in the pseudoknot enhances the structural compactness and

mechanical stability. The −1 frameshifting efficiency is positively correlated with one-step unfolding rupture force

and inversely correlated with the unfolding rate, consistent with the fact that ribosome is a force-generating

molecular motor with helicase activity.

关键字:RNA pseudoknot,Ribosomal frameshifting,Optical tweezers


56

Direct observation and ligand regulation of oligomeric state of CXCR4-EGFP

on the membrane of living cells

劳军，songyanzhuo，葛保胜，黄方，HeHua

China university of petroleum





摘要

Dimmerization or even higher order of oligomerization is a key feature of many G protein coupled receptors

(GPCRs), which regulates the functions of GPCRs and provides a unique scenario for the rational design of new

therapeutic drugs. However, it is still difficult to characterize the oligomeric status of GPCRs in living cells and

not yet clear how binding ligands regulate this status. In this work, with single molecular photobleaching, we have

investigated the oligomeric status of CXCR4, an important member of GPCRs, on the membrane of living

mammalian cells and have explored how binding ligands regulate the oligomeric status. It is found that the

oligomeric status of CXCR4 strongly depends on its expression level. CXCR4 mainly exists as monomers when its

expression level is as low as that in healthy mammalian cells. While CXCR4 turns to a mixture of monomers,

dimers and oligomers when its expression level increases to that of native tumor cells. Different types of ligands

showed various influence on the oligomerization of CXCR4. Both SDF-1α and AMD3100 could significantly

promote the dimerization and oligomerization of CXCR4 on the membrane of living cells, with the full agonist

SDF-1α more efficient than antagonist AMD3100, whereas reverse agonist TC14012 induced dissociation of

dimers and oligomers. These results suggest that the regulation of CXCR4 functions by binding ligands may be

realized through a way of adjusting the oligomeric status apart from conformational changes .

关键字:single molecule imaging,CXCR4


57

两种金属钌配合物的设计合成及其与 DNA 的相互作用研究

尹盼盼

同济大学

摘要

端粒和端粒酶与癌症之间关系密切。在正常体细胞中，端粒会随着细胞分裂而逐渐缩短，而在大部分肿瘤

细胞和癌细胞中，端粒通过端粒酶得到加长，弥补了其在正常细胞分裂中的损失，使得癌细胞能够无限分

裂而得以永生。研究表明，端粒末端形成的 G-四链体（G4）能够有效抑制端粒酶的活性，这使得 G4 成为

抗癌药物的一个重要靶点[1]。那些能够稳定 G4 结构的分子成了潜在的抗癌药物[2]。我们以 5-醛基-1,10 菲

罗啉为基础合成并表征了一系列钌多吡啶配合物：[Ru（bpy）2mbip]2+,a1；[Ru（phen）2mbip]2+,a2；[Ru

（bpy）2pbt]2+,b1；[Ru（phen）2pbt]2+，b2；[Ru（bpy）2PT2]2+，c1；[Ru（phen）2mbip]2+,c2；[Ru（bpy）

2PT3]2+,d1；[Ru（phen）2PT3]2+，d2。并通过荧光光谱、紫外可见光谱、圆二色谱和热稳定性数据得出

这八种配合物都能够稳定端粒 G-四链体，可作为潜在的抗肿瘤药物。

关键字:G-四链体,端粒,端粒酶,钌配合物


58

生物膜界面化层层组装微胶囊

邵婧鑫 , 戴陆如 , 贺强

哈尔滨工业大学、国家纳米科学中心

国家纳米科学中心


摘要

利用层层自组装技术制备金纳米棒掺杂的天然聚合物微胶囊，通过组装层数及金纳米棒的密度实现微胶囊

相应性质的有效调控。基于脂质体融合方法能够构筑生物膜界面化的聚合物微胶囊，不仅可以实现微胶囊

的功能化，进一步提高生物相容性，而且可以显著降低胶囊壁的渗透性，实现胶囊内部药物的有效封装。

活体抗肿瘤实验表明，血液环境中的微胶囊能够参与循环并穿越基体的生物屏障，富集在肿瘤部位。高强

度近红外激光照射下，可快速激发胶囊壁内大量富集的金纳米棒产生基于光热效应的气泡，气泡的破裂会

造成肿瘤组织不可逆的损伤和瓦解，实现抗肿瘤的目的（Fig. 1A）。此外，当微胶囊的中空结构载有抗肿

瘤药物时，低能量近红外激光的照射可以快速破坏生物膜和胶囊壁的有序结构，实现内载药物的快速释放，

达到基于药物的活体抗肿瘤治疗目的（Fig. 1B）。

关键字:层层自组装,聚电解质微胶囊,光热气泡治疗,可控释放,活体抗肿瘤


59

6 月 16 日下午主会场报告（8:30-9:50）

Vinculin mediated mechanosensing at focal adhesions

严洁

National University of Singapore

摘要

Force sensing is crucial for cells to regulate their adhesions to extracellular matrix (ECM) through integrin based

focal adhesions (FA). Vinculin is a crucial protein mediating mechanosensing at FA through binding to talin, a

force-bearing cytoplasmic adapters that links FA to actin network. The vinculin’s mechanosensing function relies

complex interactions with its many binding partners, which however are suppressed due to a strong interaction

between the vinculin head domains (D1-D4) and the tail (Vt) domain. It has been hypothesized that binding of the

vinculin D1 (VD1) domain to mechanically stretched talin is needed for releasing the auto-inhibited conformation

of vinculin. Here we tested this hypothesis by direct single-molecule measurements of force-dependent binding of

full-length vinculin to mechanically stretched talin, and confirmed it by showing that this binding can stabilize

vinculin in a D1-Vt dissociated state at > 5 pN forces that expose the cinculin binding sites (VBS) in talin.

关键字:Mechanosensing,Focal adhesion,Vinclulin,Talin,alpha-catenin


60

Kinetic rates versus quantum dissipation

严以京


摘要

Most of the commonly used kinetics rate theories deal with elementary single-step events and the underlying rate

constants. These are the kind coarse-graining treatments, applicable to the events that occur in the time and length

scales longer than quantum coherences. On the other hand, biophysical chemistry is concerned with

cofactors-proteins complexes that are nano-structured and also dynamically fluctuated. Quantum coherences

between different cofactors and their couplings with surrounding proteins may play important roles there. In this

talk, I will present two advanced approaches to complex kinetics rates problems, together with a few remarkable

consequences due to the quantum nature of bio-molecular systems.

关键字:kinetic rates,quantum coherences


61

6 月 16 日上午分会场报告 a（10:10-12:10）

肝脏免疫的力学-化学耦合

龙勉、章燕、吕守芹、李宁

中国科学院力学研究所生物力学与生物工程中心

摘要

血流剪切作用下白细胞与血管内皮细胞相互作用可调控炎症反应、肿瘤转移等病理生理过程。细胞表面粘

附分子与其配体间的反应动力学和力学强度所决定，体现为典型的力学-化学耦合特征。肝脏微循环具有复

杂的肝血窦结构，其中多种肝系细胞与外周血细胞在三维环境下发生相互作用，对于肝脏功能的实现至关

重要。本文采用细胞-分子生物力学实验、细胞相互作用理论模型与分子动力学模拟、生物学验证相结合的

策略，针对细胞的粘附、迁移、转运的动力学行为及其分子调控机制等问题开展研究，以期通过典型实例

诠释力学原理和方法对认识生物医学问题的可能作用。


62

RHAU 解旋酶水解 ATP 解链 G-四链体 DNA 的工作机制的研究

游慧娟, LattmannSimon , RhodesDaniela , 严洁

Mechanobiology Institute, National University of Singapore

NTU Institute of Structural Biology, Nanyang Technological University

NTU Institute of Structural Biology, Nanyang Technological University

Mechanobiology Institute, National University of Singapore

摘要

RHAU helicase specifically resolves thermodynamically stable four-stranded G-quadruplex (G4) structures that

are implicated in a wide array of biological processes. Importantly, RHAU has been suggested to be a major

source of G4 resolving activity in cells. Through direct probing the G4 stability at single-molecule level, we show

that binding of RHAU stabilizes G4 in the absence of nucleotide, while it destabilizes G4 when coupled to ATP

hydrolysis. We also show that the unfolding kinetics of a G4 structure can be modulated by different ATPase states

of RHAU. These findings provide important insights into the ATP-dependent RHAU-mediated G4 destabilization

mechanism.

关键字:解旋酶,G-四链体,单分子磁镊


63

肿瘤治疗过程中细胞迁移的生物力学研究

姚立


摘要

近年来研究表明，物理作用和机械力的作用在肿瘤细胞的生长和转移过程中起到至关重要的作用。目前对

细胞机械性能的研究大部分集中在单分子水平或单细胞水平研究细胞的粘附力等，而结合生物学现象或生

物学功能来研究集体细胞的物理作用和机械性能的较少。众所周知，肿瘤治疗最大的困难是肿瘤产生抗药

性，少量抗性细胞的产生可以改变临床上肿瘤治疗的效果。科学家还发现在肿瘤治疗的过程中，治疗引起

的少量抗性细胞会促进肿瘤的抗药性而引起肿瘤的快速增殖和转移。然而对肿瘤细胞在治疗过程中细胞物

理机械力学性质的改变鲜有报道。我们从物理化学的角度出发，利用超低场生物力谱研究在治疗过程中肿

瘤细胞的物理作用或者机械力学的改变，特别研究当产生少量的抗性细胞的时候，这些少量的抗性细胞对

整体肿瘤的物理作用和机械力学性质的影响，并初步考察其影响机理。结果表明，当产生少量的抗性细胞

的时候，肿瘤细胞的迁移速率和粘附力会显著增强，特别是在长期的药物治疗过程中。这也在进一步的活

体水平肿瘤治疗模型中得到证实。从物理化学的角度揭示治疗过程肿瘤细胞的物理机械力学的改变可以为

肿瘤的治疗提供新的视窗。

关键字:细胞迁移,生物力谱,肿瘤治疗


64

单分子力谱技术检测凝集素与细胞表面糖之间的相互作用

蔡明军 , 赵伟栋 , 徐海娇 , 蒋俊光 , 王宏达

中国科学长春应用化学研究所





摘要

糖类在很多生物过程中发挥着重要的作用。糖类可以增强蛋白的稳定性，也可以将一些蛋白固定到细胞膜

上。糖类是细胞-细胞之间，细胞-细胞外基质之间相互作用的特异性靶点。糖类分子在生物学过程中发挥

着重要的作用。糖结合物（包括糖蛋白和糖脂）在免疫防御、细胞生长、寄生虫感染、细胞之间的识别和

粘附等生物学功能上发挥重要作用。糖类的改变与肿瘤转移和类风湿性关节炎等多种病理过程密切相关。

凝集素可以和糖类特异性的结合，它们之间的作用是糖生物学研究的基础。生物分子内或分子间作用力在

分子结构、分子识别和分子动力学上具有重要的作用。基于原子力显微镜的单分子力谱技术是研究这些作

用力的重要工具。单分子力谱可以检测针尖上修饰的分子与样品中的相应分子之间的作用力，检测的灵敏

度可以达到皮牛级。应用此技术将有利于研究其它糖-凝集素或配体-受体之间的作用，并且也将有利于对

肿瘤转移、发展和入侵的研究。

关键字:原子力显微镜,单分子力谱


65

用单分子荧光手段阐释翻译过程动力学及分子机制

陈春来

清华大学

摘要

核糖体是所有生命体中合成蛋白质的生物大分子。阐释其在蛋白质翻译过程中的动力学性质，一方面可揭

示重要生命过程的分子机制，而另一方面也将有助于认知和优化以核糖体为靶点的抗生素。延伸因子

elongation factor G (EF-G)是细菌内最为保守的蛋白之一。其主要功能是高速准确地催化转运过程，既 mRNA

和 tRNA 在核糖体内的移动。然而 EF-G 在核糖体上的构型变化及其催化转运的工作机制等重要问题仍然不

清楚。利用单分子偏振全内反射荧光显微镜（polarized TIRF microscopy），首次直接观测到 EF-G 在催化

转运过程中的动态构型变化。同时我们还发现抗生素 viomycin 和 spectinomycin 可减弱但无法消除 EF-G 在

核糖体上的运动。综合以上结果，我们提出 EF-G 在催化转运过程的初期采用的是动力冲程（power stroke）

的工作机制，而在转运过程的后期采用布朗棘轮（brownian ratchet）的工作机制。核糖体和 EF-G 结合两种

不同的机制以确保转运这一动态过程的速度和精度。 Oncocin 是一类从昆虫 Oncopeltus fasciatus (milkweed

bug)中分离的富含脯氨酸的抗菌短肽。然而其抗菌机制仍然不明确。近期的研究表明 Oncocin 在细菌内与

核糖体有较强的结合能力，并可在体外翻译体系中显著地抑制蛋白的合成。通过对核糖体和 tRNA 进行荧

光标记，利用单分子荧光共振能量转移(FRET)的手段可细致观测翻译过程中的动力学过程。我们发现

Oncocin 主要影响酰胺化的 tRNA 进入核糖体。当初生肽链较短时，Oncocin 提高了同源(cognate)tRNA 在校

验(proofreading)过程中的解离速率，因而降低了 tRNA进入核糖体的速度并提高了此过程中GTP的消耗量。

而当初生肽链较长时，Oncocin 可完全阻碍 tRNA 的进入。我们的工作揭示了 Oncocin 采用多种机制抑制核

糖体功能，这将有助于开发新型的抗生素药物。本人在清华大学开展的工作获得了国家自然科学基金委、

清华-北大生命科学联合中心、及北京结构生物学高精尖创新中心的经费支持。

关键字:单分子,荧光,核糖体


66

6 月 16 日上午分会场报告 b（10:10-12:10）

利用 DNA 组装结构调控酶级联反应

刘冬生

清华大学

摘要

细胞内绝大多数生化反应，都是由多个酶催化完成的级联反应。酶协同高效地保证了细胞进程有序进行。

酶在细胞内限域环境中的特定排布是这类反应能够高效专一进行的重要原因。同时生物体通过调控酶促反

应的底物、中间产物及终产物等物质传输来调节酶级联反应的效率 1。由于此前一直缺少在体外对酶进行

定位定量组织排布的有效手段，因此如何构建体外平台以模拟细胞内环境、研究及调控酶级联反应进而探

索生命过程的分子水平机制，仍然是一个重要的科学问题。 DNA 纳米结构具有可编程性、精确的可寻址

性和可修饰性，因此 DNA 组装结构可以作为一个崭新而高效的平台，用以在体外组织酶级联反应及研究

纳米尺度上物质传递和能量运输 2。这里，我们首先将发生级联的酶分别固定在镊子状 DNA 分子机器的

两臂末端，通过驱动 DNA 分子机器的开合在纳米尺度精确地调控两酶之间的距离，影响中间产物传输途

径来调节酶级联反应效率 3。同时，为了进一步模拟细胞内受限环境，探究物质的受限扩散对酶级联反应

的影响，我们利用 DNA 纳米技术构建管状限域体系，结合骨架的定位能力研究了限域环境中物质扩散对

酶级联反应效率的影响 4。

关键字:DNA 组装,级连反应


67

Effect of Molecular Geometry on the Self-Assembly of Peptide Isomers and

Their Application as DNA Vectors

曹美文 , 赵文静，谢子龙，徐海

China University of Petroleum (East China)




摘要

A series of surfactant-like peptides are designed and synthesized. Taking advantage of peptide’s versatile

molecular design, six peptides that have the same amino acid composition but varied molecular geometries are

synthesized by simply varying the primary sequence. For each peptide, the polar head is made of three repeated

lysine (K) residues while the nonpolar part is a twelve-residue hydrophobic tail consisting of repeated glycine (G),

alanine (A), valine (V), and isoleucine (I) residues. Since the side chain groups of these residues are different in

size and hydrophobicity, their positional change leads to molecules with different geometries, that are, the

cone-like peptides of G3A3V3I3K3 and K3I3V3A3G3, the dumbbell-like peptides of I3V3A3G3K3 and

K3G3A3V3I3, and the random-sequenced peptides of V3G3I3A3K3 and K3A3I3G3V3. Study on self-assembly

of these peptides showed that the cone-like peptides self-assembled into short nanorods, the dumbbell-like peptides

formed sheet-like structures, while the random-sequenced peptides produced regular long fibrils. The results

clearly demonstrate that the molecular geometry plays a dominant role in determining the final self-assembled

structures. Further experiments showed that these molecules, except V3G3I3A3K3, all exhibited excellent DNA

condensing ability. Specially, I3V3A3G3K3 could condense λ-DNA (~16 μm in length) into well-structured

nanoassemblies (~200 nm in diameter) in which the DNA molecules are orderly aligned and packed. Experiments

also revealed that the V3G3I3A3K3/DNA complexes exhibited excellent anti-enzymatic hydrolysis ability and

could deliver DNA molecules efficiently into cells.

关键字:peptide self-assembly,DNA condensing


68

软物质纳米组装体的亚细胞定位机制

吴富根 , 贾浩然 , 王宏银 , 李艳红 , 蒋耀文 , 陈晓凯 , 潘光玉 ,

ChenZhan

东南大学生物科学与医学工程学院，生物电子学国家重点实验室，南京市四牌楼 2 号，210096







Department of Chemistry, University of Michigan

摘要

生物高分子和脂质体是目前安全性最好的药物载体。研究由生物高分子和脂质分子形成的纳米组装体与细

胞的作用机制，尤其是与不同细胞器（包括细胞膜、溶酶体、线粒体、高尔基体、内质网等）的动态作用

机制，对于设计和优化新型的药物载体，进而提高药物的药效，具有重要的意义。本报告将围绕由生物高

分子和脂质体组成的软物质纳米组装体，汇报如下进展：（1）不同相态和组分的脂质体与细胞的作用机制。

我们发现凝胶相的脂质体易被细胞内吞，胆固醇的加入可以减少脂质体被细胞物理吸附。聚乙二醇化之后

的脂质体则可以改变脂质体被细胞吞噬量和在细胞内的定位。（2）生物高分子与模型细胞膜（支撑双分子

层膜、巨型囊泡）以及活细胞的作用机制。我们设计开发了一系列可以锚定到细胞膜上的生物高分子，从

而实现了对细胞膜的成像以及基于细胞膜的肿瘤光动力学治疗。同时，通过精密调控生物高分子的结构，

使之带有适度的正电荷和疏水锚定基团，通过其能够在水溶液中的发生自组装及在接触细胞表面时发生解

组装的性质，可以实现对不同类型的细胞（包括动物细胞、细菌、真菌）等的普适性成像。此外，我们利

用生物高分子的正电荷和疏水染料分子，开发出了特异性地标记脂筏（lipid raft）的试剂。（3）脂质体包

裹可以改变染料分子的亚细胞定位机制。我们发现染料分子被脂质分子包裹在脂质体中后，其在细胞内的

定位机制发生了巨大改变，从而我们成功开发出了特异靶向到线粒体的荧光探针及药物载体。

关键字:细胞内吞,亚细胞定位,细胞膜,生物高分子,脂质体


69

含核苷类抗癌药物 DNA 纳米结构的构建及其与细胞相互作用

张川

上海交通大学

摘要

传统纳米药物输送体系（例如聚合物，脂质体，无机纳米粒子等）负载抗癌药物时通常具有纳米粒子粒径

分散度高、批次重复性差的特点，其化学组成、形貌、尺寸难以得到精确控制，因而难以有效地阐明其与

生物体系相互作用时的规律和分子机制，限制了纳米药物输送体系在相关疾病治疗领域的应用。基于核苷

类似物抗癌药物分子与天然核苷单体结构的相似性，同时受自然界核酸分子组成及其组装原理的启发，我

们将具有抗癌作用的核苷类似物药物分子通过化学以及生物的方法修饰整合到具有优异分子识别及组装功

能的核酸分子上，然后利用 DNA 纳米技术实现了一系列具有精确组分和形貌的含药核酸纳米结构的构建，

进而将其作为新型纳米药物输送体系用于癌症治疗的研究。对于整合了核苷类似物药物分子的不同 DNA

精确纳米结构，我们通过改变组装体的尺寸以及形貌研究其与细胞的相互作用，从而揭示不同结构因素对

细胞摄取、胞内转运的影响，阐明该新型含药纳米结构与细胞作用时的构效关系，为开发更安全高效的纳

米药物输送体系提供新的路径。

关键字:纳米药物,DNA 纳米技术,核苷类似物,细胞摄取


70

基于自然纤维素物质的仿生纳米材料用作锂离子电池电极的研究

黄建国

浙江大学化学系

摘要

自然生物物质是构建人造功能纳米结构材料理想的模板和支架[1]。高容量和高循环稳定性的锂离子电池负

极材料近年来引起关注，选择合适的具有高比容量和结构稳定性的非碳基材料对于提高电池性能是重要的。

基于此，应用表面溶胶−凝胶方法在纤维素物质的纳米纤维表面以纳米级别的厚度可控沉积金属氧化物凝胶

薄膜，并进行相应的后续处理，合成了系列硅、二氧化钛和二氧化锡纳米管，以其碳或者共轭聚合物复合

材料用作锂离子电池负极，研究了相应的电极性能[2−5]。所制得的的材料继承了起始纤维素物质的多孔结

构，为缓解电极材料在充放电循环中的体积变化提供了有效的缓冲空间；另外，复合材料中纤维素碳化而

来的碳纤维亦对材料体积变化提供了缓冲介质；导电聚合物等的引入作为缓冲层和提高材料导电性，也有

效改善了电极的性能。以自然纤维素物质为模板或支架构筑纳米结构金属氧化物（复合）材料为新型高性

能锂离子电池电极材料的开发提供了可能。关键词：仿生材料；纳米材料；模板合成；自组装；薄膜参考

文献： [1] Li, S.; Huang, J. Adv. Mater. 2016, 28, 1143. [2] Wang, M.; Li, S.; Zhang, Y. Huang, J. Chem. Eur. J.

2015, 21, 16195. [3] Li, J.; Huang, J. Chem. Commun. 2015, 51, 14590. [4] Li, S.; Huang, J. J. Mater. Chem. A

2015, 3, 4354. [5] Wang, M.; Jia, D.; Li, J.; Huang, J. RSC Adv. 2014, 4, 33981.

关键字:仿生材料,纳米材料,模板合成,自组装,薄膜


71

6 月 16 日上午分会场报告 c（10:10-12:10）

超分辨率活细胞成像技术进展

李栋

Institute of Biophysics

摘要

超分辨率显微镜在 20 年的发展过程中，基于不同的物理原理和荧光标记分子的光调控特性，已经发展出多

种在理论上可以达到远小于衍射极限分辨率的方法。但需要注意的是，在对活体生物样品进行连续成像时，

许多方法却面临着严重的局限和挑战，例如，需要的成像时间过长以至于活体样品中微结构的运动位移已

经大于所能达到的分辨率，导致最终图像模糊；或者需要的照明光功率过高(MW/cm2 到 GW/cm2)，导致

生物样品的损伤，等等。结构光照明显微技术（structured illumination microscopy，SIM）被实验证明可以

比较均衡地满足活体成像的各项指标，因为相对与其他超分辨率技术而言，SIM 需要的原始图像数目较少，

同时要求的照明光功率较低（W/cm2），以及其光学系统的传递函数对高分辨率信号的传递效率较高等等。

但是，SIM 最大的缺陷在于其仅能提供两倍的分辨率提高，达到 100nm 左右。在这个报告中我将讲述最新

发展的两种提高SIM分辨率的方法，使其达到 100nm以下分辨率，同时保持其对活体生物成像的独特优势。

关键字:超分辨率显微镜技术,活细胞成像


72

化学交联质谱分析用于蛋白质动态结构的研究

刘主

浙江大学

摘要

蛋白质通过结构的动态变化执行其多样的生物学功能，解析蛋白质的动态结构、阐明蛋白质不同结构之间

的相互转换过程可以揭示其行使功能的分子机制。由于动态的蛋白质的结构的能量高、存在时间短，常规

的生物物理化学手段不易捕获，其动态结构的研究手段还比较缺乏、方法尚待完善。通过发展蛋白质化学

交联质谱分析技术（CXMS），我们成功解析了多种蛋白质的动态结构、蛋白-蛋白复合体的中间态，描述

了它们在执行功能过程中的动态变化。选用带有活性基团的化学交联剂，将其加入到蛋白质溶液中进行蛋

白质的交联。这些交联剂可与蛋白质中的特定氨基酸形成稳定的酰胺键，两两交联，由于交联剂的长度一

定，因此只有当参与交联的两个氨基酸的距离合适时（小于交联剂的长度），它们才能被交联剂交联，对

交联产物进行质谱分析，可指认蛋白质中被交联的氨基酸残基。由于交联对体现的是两个氨基酸之间的距

离信息，基于此，我们发展相关的计算方法，建立了基于 CXMS 数据快速计算、评估蛋白质动态结构的方

法。CXMS 技术对蛋白质的分子量没有限制、纯度要求不高、不需要对蛋白质进行特殊的化学标记，可快

速获取、判别蛋白质的动态结构和分布，广泛应用于蛋白质动态结构和功能的研究。

关键字:蛋白质,动态结构,化学交联,质谱,蛋白质功能


73

核酸分子-细胞膜作用过程中磷脂双层膜的电荷反转与重构

魏锋 , 李雯慧 , 郑万泉

江汉大学交叉学科研究院

江汉大学交叉学科研究院

巴黎第十一大学分子科学研究所

摘要

界面核酸分子的结构与动力学是决定核酸药物稳定性与功效的关键。本实验室研发了一套偏振分辨和频振

动光谱（SFG-VS）系统用于生物界面的原位、实时、免标记的检测。利用该光谱检测系统，我们对核酸分

子在层状正电荷 DMTAP 磷脂双层膜上的分子构相与吸附动力学进行了研究。PO2−波段，OH/NH 波段和“指

纹区”波段的光谱数据显示，核酸分子的吸附在 375 nM（ρ ≈ 3.75）达到饱和，取向角也趋于稳定。吸附动

力学的数据也表明核酸分子在 DMTAP 双层膜上的吸附会导致界面氢键结构的破坏与方向反转。这些在分

子层次上对核酸与生物膜相互作用的新理解，将有助于核酸相关药物与传感器的开发与性能改进。

关键字:偏振分辨检测,层状磷脂双层膜,“指纹区”光谱,吸附动力学


74

Computational design of peptide-Au cluster probe for αIIbβ3 integrin

detection and quantification in single cells

赵丽娜

中国科学院高能物理研究所

摘要

Integrin is related to many major diseases (such as cancer and thrombus) tightly, which serves as the molecular

marker to these diseases. Quantitatively targeting detecting integrin can diagnose these diseases in early stage and

support sufficient treatment timely. While it is difficult to screen the gold fluorophore binding ligand efficiently in

the experimental targeting probe design. In this work, we have designed a novel peptide-Au cluster probe by

theoretical method to specifically bind to IIb3 integrin. As indicated by molecular dynamics (MD) simulations,

the peptide-Au probe can provide multiple coating peptides to form additional salt bridges with protein, and the

binding stability of the probe is comparable to the native ligand of IIb3 integrin. The designed probe then can be

successfully synthesized. We have realized the spatially marking of IIb3 integrin by the colocalization analysis

of confocal microscopy. Additionally, we also realize the quantitatively counting of IIb3 integrin via this novel

peptide-Au cluster probe. On single cell level, we find the number of IIb3 integrin ranges from 5.75 to

9.11×10-17 mol for the heteroexpression of individual cells. It is helpful for estimating the disease progression for

diagnosis and detecting the drug response for therapy. In conclusion, our results suggest the combination of

computational design and experimental verification can be a useful strategy for the development of nanoprobes.

关键字:peptide-Au cluster,molecular dynamics,single molecular detection


75

上转换荧光分析方法及生物应用

李贞 , 刘志洪



摘要

上转换发光材料(UCNPs)是一类稀土掺杂的发光材料，可以连续吸收两个或多个近红外(通常为 980 nm) 的

光子，发出可见光。在近红外光的激发下，可以很好地消除来自生物样本的本底荧光和散射光的干扰。另

外，在 980 nm 激发下，可以有效避免受体被直接激发【1,2】。因此，UCNPs 是一类很有前途的 FRET 供

体材料。与此同时，FRET 原理通过发光猝灭-恢复的检测模式提升信/背比，很好地弥补了 UCNPs 发光量

子效率不足的问题。 UC-FRET 自 2005 年提出以来【3】，已应用于许多领域。能量转移效率一直是该领

域的关键问题，也是制约分析方法灵敏度的重要因素。以小分子染料做能量受体的 UC-FRET 技术，能量

转移效率通常不高，供体荧光很难猝灭，导致灵敏度不高，分析性能受到一定影响。为了提高 FRET 效率，

我们在近几年中从两方面做了一些探索。一方面，我们发展了一系列新的纳米材料能量受体，如石墨烯，

碳纳米颗粒，二维原子晶体，贵金属原子簇等。这些无机纳米材料的表面能量转移以及电子转移机制使得

有效的能量转移距离提高至 20-30nm，显著提高了 UC-FRET 体系的能量转移效率(>80%)。另一方面，基于

FRET 对供-受体距离的高度依赖性，我们着眼于革新 UCNPs 结构。通过构建夹心、非均质的材料结构，将

发光的稀土离子限域在尽可能接近纳米颗粒表面的薄层内，从而提高 FRET 效率。在这些材料的基础上，

建立了一系列基于 UC-FRET 原理的传感平台和探针，实现复杂生物样品(如血液)的均相检测(mix-and-read)

以及细胞、组织成像分析【4-10】。

关键字:上转换荧光,生物应用


76

6 月 16 日下午分会场报告 a（14:00-16:00）

Protein dynamical structures and their relevance to biological function

revealed by time-resolved temperature-jump transient IR spectroscopy

翁宇翔

Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China

摘要

Dynamical Protein structure in vivo is generally different from that of “frozen” crystal structure. Exploring

protein dynamical structure is not only imperative to elucidate its biological function, but is also important to

understanding the fundamental problems such as protein folding. In this talk I’ll present some of our recent

progresses in elucidating the protein dynamical structural changes and their relevance to the biological functions

by using temperature-jump time-resolved mid-IR transient absorbance difference spectroscopy, a powerful tool to

trace the changes of secondary structures in thermal-induced folding/unfolding dynamics of proteins.

To achieve a better detection limit in the thermal induced optical density change, we recently constructed a

Q-switched Ho:YAG nanosecond laser which delivers a fundamental output of 2.01 mm as the heating laser for

D2O, the spatial beam profile and the temporal stability of Ho:YAG laser are more stable than those of Raman

converter made of high pressured hydrogen cell. The probe beam is a cw CO laser covering amide I region with a

spectral width of 4 cm-1.1 We have successfully used this method to investigate the dynamical structural change

of a number of proteins including disulfur bond isomerase DsbC 2 and heat shock protein Degp,3 and their

relevance to the biological function of proteins.

1. Li, D.; Li, Y.; Li, H.; Wu, X.; Yu, Q.; Weng, Y., A Q-switched Ho: YAG laser assisted nanosecond

time-resolved T-jump transient mid-IR absorbance spectroscopy with high sensitivity. Review Of Scientific

Instruments 2015, 86(5).

2. Li, H.; Ke, H.; Ren, G.; Qiu, X.; Weng, Y. X.; Wang, C. C., Thermal-Induced Dissociation and Unfolding of

Homodimeric DsbC Revealed by Temperature-Jump Time-Resolved Infrared Spectra. Biophysical

Journal 2009, 97(10), 2811-2819.

3. Li, S.; Wang, R.; Li, D.; Ma, J.; Li, H.; He, X.; Chang, Z.; Weng, Y., Thermal-triggerd Proteinquake Leads to

Disassembly of DegP Hexamer as an Imperative Activation Step. Scientific reports 2014, 4, 4384.

http://mail.ustc.edu.cn/coremail/s/preview/~4leKttjsPkU5tJs1NVOA1e5u3mMNR1IyaKy4tExwavY=~/1:1tbiAQYQE1QhmKembgAdsb/OrHx/_10315.html#_ENREF_1




77

Studies on Conformation changes of biomolecules by Terahertz

time-domain spectroscopy

颜识涵 , 张明焜 , 魏东山

中国科学院重庆绿色智能技术研究院



摘要

Terahertz (THz) wave refers to the frequency ranging from 0.1 to 10 THz. THz radiation excites low-frequency

molecular vibrations from intra/inter-molecular domains connected by the weak interactions including hydrogen

bonds, van der Waals and non-bonded (hydrophobic) interactions etc. The energy level of THz wave largely

coincides with the level of the biomolecular low-frequency motions such as vibration, rotation and translation of

the molecular skeleton. These movements which are close correlated with the conformation changes of

biomolecules can be identified through fingerprint features in the THz transmission or absorption spectrum.

Furthermore, the energy of THz wave is relatively low with a value of ~4 meV per photon, which will hardly cause

the ionizing damage to the structure of biomolecules. Therefore, THz spectroscopy can be used as a label-free and

efficient technique to detect the conformation change of biomolecules. Here we presented the THz time-domain

spectroscopy technology to investigate the conformation changes of surfactants and lipid molecules at different

concentrations and DNA molecules at different confinement conditions. Conformation changes were detected by

observing the variations of optical parameters at the THz frequency range including the absorption coefficient,

refractive index and dielectric constants etc. which were explained from the hydration of biomolecules.

Correspondingly, the critical concentration to form micelles or lipid bilayers and the critical confinement size were

determined according to these variations.

关键字:Terahertz spectroscopy,conformation change,surfactant,lipid,DNA


78

微流控芯片高通量单细胞分泌蛋白分析

陆瑶，FANRONG

中科院大连化学物理研究所

Yale University

摘要

细胞是生命存在的基础，探索生命健康与疾病常需要以细胞研究为基础。由于细胞与细胞之间存在差异，

群体细胞的研究结果只能得到一群细胞的平均值，这往往会掩盖个体差异信息。为更全面的了解细胞以服

务人类健康、疾病研究，单细胞分析就变得尤为必要。单细胞分析的一个核心难点在于如何实现对单个细

胞的精确操控（如捕获、刺激、检测等），这往往是传统的生物学技术较难实现的。微流控学作为一种针

对微量流体进行精准操控的系统科学技术，其微米级通道的空间尺寸非常符合单细胞的结构特点，更加有

利于实现在微小尺寸、体积下的各种细胞操作。这不仅可以提高单细胞分析的通量和检测灵敏度，而且可

以实现更加复杂、集成的细胞操作和对其更加优化的时间、空间控制。目前微流控芯片正在快速的整合入

单细胞分析技术的研究中，并发挥越来越重要的作用(1)。我们设计开发了一种高通量、高内涵单细胞蛋白

分析平台，可对数以千计的活体单细胞所分泌的 42 种蛋白分子分别进行同时检测。我们利用这一平台深入

系统地研究了人体免疫细胞巨噬细胞（macrophage）在不同 TLR（Toll like receptor）配体刺激下的单细胞

免疫应答。研究揭示：人巨噬细胞在同一 TLR 配体刺激下的免疫应答呈现丰富而有规律的异质性

（heterogeneity），其对于刺激的应答取决于细胞本身状态；按照人巨噬细胞在同一 TLR 配体刺激下的不

同蛋白分泌响应可将其主要分为四种类型。这是一项利用该新技术所得到的新的生物学发现，大大加深了

人们对人体免疫力的第一道屏障——固有免疫（Innate Immunity）的认识(2)。同时我们还利用该项技术进

行了转化医学的应用研究，如尝试了对多例脑瘤手术病人的脑瘤组织样本进行了单细胞水平分泌蛋白检测、

分析(3)。参考文献 [1] Chattopadhyay PK, Gierahn TM, Roederer M, & Love JC. Nature immunology, 2014

15(2):128-135. [2] Lu Y, et al. Proceedings of the National Academy of Sciences of the United States of America,

2015, 112(7):E607-E615. [3] Lu Y, et al. Analytical Chemistry, 2013, 85(4):2548–2556.

关键字:单细胞分析,分泌蛋白,细胞异质性,微流控芯片


79

溶液顺磁弛豫增强用于蛋白质结构和动态学研究

龚洲 , 顾新华 , 唐淳

中国科学院武汉物理与数学研究所



摘要

对蛋白质结构和动态学性质的研究是了解其功能的关键和前提。顺磁弛豫增强（Paramagnetic Relaxation

Enhancement，简称 PRE）作为一种重要的溶液核磁共振方法，在蛋白质的结构和动态学研究中取得了很多

成功的应用。然而，传统的顺磁弛豫增强方法需要对蛋白质上特定位置的氨基酸进行突变以标记顺磁探针；

同时，标记上的顺磁探针也可能对蛋白质的结构或动态性质本身造成影响。在传统的顺磁弛豫增强方法的

基础上，我们发展了溶液顺磁弛豫增强（solvent PRE，sPRE）方法，这种方法不需要在蛋白质上标记顺磁

探针，只需将顺磁探针以合适的浓度加入到蛋白质溶液样品中即可。我们对目前广泛使用的溶液顺磁探针

进行了改进，重新设计合成了新一代用于 sPRE 研究的溶液顺磁探针，可以很好的避免氢交换、蛋白质与

探针之间的相互作用等问题，从而提高实验的准确性。同时，我们发展了 sPRE 的理论计算方法和基于实

验数据对计算结构进行挑选和拟合的整合分析方法。应用新发展的 sPRE 方法，我们不仅对结构相对稳定

的蛋白质（如 GB1，泛素蛋白单体）进行了准确表征，还成功捕获到腺苷激酶在溶液中存在的部分闭合的

中间状态结构。这种 sPRE 方法能够进一步广泛应用于各类蛋白的结构和动态学研究中

关键字:核磁共振,溶液顺磁弛豫增强,蛋白质动态学


80

界面生物分子相互作用及界面振动能量传递

叶树集


摘要

界面分子间的相互作用是决定界面吸附、组装等界面现象的根源。因为分子间相互作用是一种远程的、强

度弱的作用，在实验上很难将其测量出来。如何测量界面间弱相互作用也成为一个很多人不敢碰触的难题。

本研究中，基于分子振动能量转移理论，我们发展了分子间弱相互作用的测量技术。理论上，当分子的某

一弯曲振动的倍频与另一振动的基频能量接近时，二者发生共振而导致倍频峰从基频峰借取能量，该过程

叫费米共振。费米共振在分子光谱中起很重要作用，其特征的突出强烈依赖于耦合强度和混合态间的能级

差。而后者则受分子间相互作用影响。根据此概念，我们发展新方法来精确测量界面分子的二阶费米共振

信号，发展出能表征界面弱相互作用的新技术。以磷脂分子为模型，通过改变磷脂分子链长和分子间距离

来调控界面弱相互作用，建立了费米共振峰/基频峰强度比(R)与弱相互作用之间的关系。通过研究不同离子

对磷脂分子费米共振的影响，获得了离子影响界面弱相互作用的规律，即离子在减弱范德华作用的同时，

大幅度改变界面分子水合作用。应用该技术，我们详细研究了磷脂分子在相变过程中的弱相互作用变化。

在相变过程中，磷脂头部和尾部的不协同变化导致磷脂尾部聚集，从而大幅度增加范德华相互作用。在此

基础上，我们发展了振动态选择激发-和频光谱探测的飞秒时间分辨测量技术，发展出能测量各个弱相互作

用的新方法，形成一套有效的表征界面总的弱相互作用以及各个弱相互作用的新技术。我们系统研究了

alpha-螺旋多肽分子 WALP23 在不同氢键条件下的酰胺键中 N-H 振动的超快能量转移过程。WALP23 分

子部分插入到生物膜时候，存在酰胺键与 H2O 之间、酰胺键与酰胺键之间的氢键结构，此时 N-H 驰豫时

间为 1.1(+/-0.1)皮秒；当多肽分子全部插入到膜时候，酰胺键与 H2O 之间的氢键结构减少、酰胺键与酰胺

键之间的氢键结构增加，驰豫时间变为 1.4(+/-0.1)皮秒。但当我们用 D2O 把暴露在磷脂头部的 N-H 氘代成

N-D 后，只存在酰胺键与酰胺键之间的氢键结构，留在疏水区域的 N-H 的驰豫时间变成 2.0(+/-0.1)皮秒，

随后激发 N-H（酰胺 A 谱带），分别探测 C=O（酰胺 I 谱带）和 C-N 振动（酰胺 III 谱带），清楚看到能

量通过酰胺键之间的氢键转移到 C=O 键上，而不是通过酰胺键内的偶合作用传递。该研究不仅区分了不同

环境下的氢键作用，还揭示了氢键作用在膜蛋白能量传递途径和速率中的作用。

关键字:时间分辨和频光谱,界面振动能量转移,分子间相互作用,分子间偶合作用,膜蛋白


81

6 月 16 日下午分会场报告 b（14:00-16:00）

Insight into the Binding of Metal Ions and Small Bioactive Molecules with

Bio-macromolecules through Crystallography

王宏飞，王文明，ZhangXinyu , PanHuifen , MaZhiou , XuLiqun

Institute of Molecular Science, Shanxi University

Shanxi University

Shanxi University

Shanxi University

Shanxi University

Shanxi University

摘要

Crystallography is an important method to determine the biological macromolecular structure at atomic resolution,

and the crystal diffraction measurement is the most direct and effective technology to solve the three-dimensional

structure of macromolecules. Knowledge gained through X-ray crystallography has fundamentally advanced our

views on cellular and life processes. Binding of metal ions with bio-macromolecules played important role in their

crystal structural determination. Hereby, several structures of metal ions binding proteins were introduced and

important contributions of metal ions for crystal structural determination was summarized. Moreover, some crystal

structures of ATP, GTP, GSH binding proteins were determined, their structures and functions were analyzed and

discussed.

关键字:Crystallography,Bio-macromolecules,Structures and functions


82

Conjugated Polymer Grafted with H2O2-Sensitive Prodrug for Cell Imaging

and Tumor Cell Killing

刘礼兵，李梦，吕凤婷，王树

Institute of Chemistry,CAS




摘要

A new conjugated polymer poly(fluorene-co-phenylene) derivative containing pendent quaternized chlormethine

(PFP-Chl) was synthesized by covalent linking small molecular prodrug groups onto conjugated polymer side

chains. H2O2-sensitive prodrug with an eight-member-cyclic boronate ester structure could suffer from

H2O2-triggered nitrogen mustard release and further DNA cross-linking and alkylation. PFP-Chl combines

therapeutic characteristic with excellent optical property of conjugated polymers. It is found that PFP-Chl could

enter into cells by endocytosis to simultaneously exhibit abilities of fluorescent imaging and tumor cell inhibition.

关键字:Conjugated Polymer,Cell Imaging,Tumor Cell Killing


83

Structural and functional of Hantavirus

nucleocapsid proteins

郭宇 , 王文明

南开大学

山西大学

摘要

Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including

humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome

(HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the

genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal

structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV),

which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV

NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic

study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding

extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in

RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region

connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through

contacts made with two adjacent protomers. This work provides insight into the formation of hantavirus RNP and

provides an understanding of the evolutionary connections that exist among bunyaviruses.

关键字:蛋白质晶体结构,核蛋白,汉坦病毒


84

Ultrastructure and mechanical perturbation of pulmonary surfactants by

inhaled carbon nanoparticles: a computer simulation study

岳同涛 , 黄方 , 徐燕




摘要

Carbon nanoparticles (CNPs), such as graphene nanosheets (GNs), carbon nanotubes (CNTs) and carbon

nanospheres (CNSs), have displayed extraordinary mechanical, electrical and thermal properties. They accordingly

have potential applications in diverse fields from energy conservation to disease therapy. In parallel, there is a

general biosafety concern for human exposure of CNPs. Since human lung is easily accessible for CNPs, the

increasing exposure of CNPs is putting human lungs at high risk. During respiration, inhaled CNPs are first

captured by the pulmonary surfactant (PS) and disrupt its ultrastructure and mechanical property. With the aid of

computer simulation techniques, we have investigated the interaction between PS and CNPs. For GNs, their

pulmonary adsorption was found to rigidify the PS and thus inhibit its mechanical function. The internalization is

generally accomplished via PS shape transformation and GN self-rotation. For CNTs, five different interaction

pathways were identified by varying the aspect ratio. They are vertical insertion, horizontal translocation, lipid

extraction, vesicle encapsulation and endocytic internalization. Each pathway displays unique behavior for PS

perturbation. For CNSs, their aggregation in PS was found to be size dependent and mediated by lipid extractions.

Future studies will be carried out by combining simulations and in vitro experiments to thoroughly understand the

inhalation toxicity of more general nanoparticles. We hope that our studies can provide guidelines for developing

effective strategies against the adverse effects of inhaled CNPs.

关键字:carbon nanoparticles,inhalation toxicity,pulmonary surfactant,computer simulation


85

Probing protein conformational dynamics by combining experimental and

computational studies

王文宁

复旦大学

摘要

Protein conformational dynamics is an indispensable part of a complete description of protein functions. The

intrinsic dynamics of proteins can be linked to their functions in several ways. In this talk, we will show some

examples of protein conformational dynamics study with combined NMR, MD simulation and smFRET methods.

For one example, we explored the inter-domain dynamics of a periplasmic binding protein in apo form with NMR,

MD simulation and smFRET, and showed that at least four conformational states exist in solution and the MD

derived structure ensemble well described the NMR RDC data. In a second example, we showed how entropic

effect due to changes in internal dynamics of multi-domain protein associated with molecular recognition and

ligand binding affinity through a study of the PDZ12 tandem of PSD95. 2 In a third one, we discovered that the

C-terminal domain (CTD) of protein 4.1 3 is an intrinsically disordered protein. By combining NMR, smFRET and

MD simulation, we obtained the conformational ensemble of CTD and CTD/NuMA peptide complex, showing

that the structure ensemble is highly dynamic and modulated by the ligand binding.

关键字:Comformational dynamics,NMR,MD simulation


86

6 月 16 日下午分会场报告 c（14:00-16:00）

蛋白质别构调控分子设计

来鲁华

北京大学化学与分子工程学院

摘要

蛋白质的别构调控是生物体系中广泛存在的功能调节方式。对于各种复杂的生物分子体系，别构调控是如

何实现的，为什么不同的蛋白质会采取不同的调控方式以及如何设计化学小分子进行蛋白质特定功能的针

对性调控等都有待深入研究。我们在生物网络和单个结点蛋白质水平上研究了别构调控的影响，发展了蛋

白质别构位点预测方法，并通过分子设计手段获得了可以上调或下调蛋白质活性的化合物，为进一步揭示

蛋白质别构调控的机理奠定了基础。参考文献： [1] Meng, H., McClendon C. L., Dai, Z. W., Li, K. N., Zhang,

X. L., He, S., Shang, E. C., Liu, Y., Lai, L. H. (2016). Discovery of Novel 15-Lipoxygenase Activators to Shift the

Human Arachidonic Acid Metabolic Network toward Inflammation Resolution. J. Med. Chem. 59, 4202-4209. [2]

Meng, H., Liu, Y., Lai, L. H.* (2015). Diverse Ways of Perturbing the Human Arachidonic Acid Metabolic

Network To Control Inflammation. Acc. Chem. Res. 48, 2242-2250. [3] Ma, X. M., Qi, Y. F., Lai, L. H. (2015).

Allosteric sites can be identified based on the residue-residue interaction energy difference. Proteins 83,

1375-1384. [4] Pei, J. F., Yin, N., Ma, X. M., Lai, L. H. (2014) Systems Biology Brings New Dimensions for

Structure-Based Drug Design. J. Am. Chem. Soc. 136, 11556-11565. [5] Qi, Y. F., Wang, Q., Tang, B., Lai, L. H.*

(2012) Identifying Allosteric Binding Sites in Proteins with a Two-State Gō Model for Novel Allosteric Effector

Discovery. J. Chem. Theory Comput. 8, 2962-2971.

关键字:蛋白质,别构调控,分子设计


87

Decoding Collagen - Computational Design of Fibrous Proteins

许菲

Jiangnan University

摘要

As the most abundant protein in human, collagen serves as a scaffold of biological processes in extracellular

connective matrix. Collagen has also been widely utilized as bioactive cell culture substrates in tissue engineering.

Here, I approach biophysical properties of collagen in two aspects (1) computational design of collagen sequences

to induce the orthogonal assembly of multiple heterotrimers via electrostatic interactions[1, 2]; (2) computational

modeling of collagen inter-helical interactions via shape complementarity to promote its higher-order assembly [3].

With these projects, we demonstrate how computational methods could help to design collagen-based biomaterials.

References: [1]. Xu, Fei, Zahid, S., Silva, T., Nanda, V., Computational Design of a Collagen A:B:C-type

Heterotrimer, Journal of American Chemical Society, 2011, 133:15260-15263 [2]. Fei Xu, Silva, T., Joshi, M.,

Zahid, S., Nanda, V., Circular Permutation Directs Orthogonal Assembly in Complex Collagen Peptide Mixtures,

Journal of Biological Chemistry, 2013, 288: 31616-31623 [3]. Fei Xu, Khan, I. J., McGuinness, K., Parmar, A. S.,

Silva, T., Murthy, S., Nanda, V., Self-assembly of left and right-handed molecular screws, Journal of American

Chemical Society, 2013, 135: 18762-18765

关键字:computational design,collagen,biomaterials


88

Developing RNA Duplex-Binding Peptide Nucleic Acids for Biotechnological

Applications

陈刚


摘要

The functions of RNA include coding (for protein, RNA, and DNA), gene regulation, catalysis, and

immunomodulation. The overall goal of Gang CHEN research group is to better understand the structures and the

physical-chemical properties of RNAs and RNA-ligand complexes to provide deeper insight into and to facilitate

precise control of the diverse biological functions involving RNA. Naturally-occurring triplexes are important for

shaping RNAs into complex three-dimensional architectures and are important for diverse biological functions. As

double-stranded RNA stem regions are often involved in biologically important tertiary triplex structure formation

and protein binding, the ability to sequence-specifically target any desired RNA duplexes (by triplex formation)

would have great potential for biomedical applications. We are developing programmable chemically-modified

triplex-forming oligonucleotides (TFOs) and triplex-forming peptide nucleic acids (PNAs) to form TFO·RNA2

and PNA·RNA2 triplexes, respectively. We have demonstrated that triplex-forming PNAs can specifically bind to

RNA duplex structures, and thus modulate protein translation and virus replication.

关键字:RNA structure,RNA recognition,RNA folding and unfolding,RNA as therapeutic targets


89

基于弱相互作用的蛋白质-多糖特异性识别机理的分子模拟研究

康玉

浙江大学

摘要

蛋白质与糖的特异性识别在生命体的信息传递、免疫应答等过程中均发挥关键作用，但目前的研究深度和

进展却远未达到人们根据其重要性所作出的预期。由于糖的结构复杂程度远远高于蛋白质等其它生物分子，

且蛋白质与糖的相互作用相对较弱，这对现有实验方法和计算机模拟策略设计来说是巨大挑战。从分子尺

度理解糖链全局结构与蛋白质-糖相互作用的关系是理解特异性识别的关键。该工作主要是以噬菌体 Sf6 尾

突蛋白与弗氏志贺菌 Y 血清型 O 抗原为模型研究对象，运用分子动力学模拟方法，结合 XRD、NMR 等实

验手段，对针对糖分子的特定力场参数和系统研究策略进行探索，研究蛋白质对多糖的特异性识别机理。

具体从四糖复合物晶体学结构出发，通过模拟和实验获得更长糖链（8-12 糖单元）与蛋白质间基于弱相互

作用的动态结合模式。研究表明，对于不同长度多糖-蛋白质弱相互作用体系，抗原表位与蛋白质关键 loop

区的构象灵活性对于复合物结合模式有重要影响。其中不同长度糖分子还原端构象灵活性及其在酶水解位

点处构象差异或为后续酶促水解反应机理研究提供重要结构信息。 Kang et al. J Am Chem Soc DOI:

10.1021/jacs.6b00240 Kang et al. J Phys Chem B DOI: 10.1021/jp4111713

关键字:糖分子结构,特异性识别,分子模拟


90

基于人工设计蛋白研究折叠协同性等序列结构规律

刘海燕


摘要

计算生物学的发展，让我们能人工设计能够稳定折叠成给定三维结构的氨基酸序列。这在蛋白质工程中有

重要应用前景，同时有助于我们从新的角度去分析、检验我们关于蛋白质结构序列规律的认识。我们将介

绍基于统计能量模型的蛋白质设计方法 ABACUS 及其实验验证；我们还将报告以人工设计蛋白为基础，对

蛋白质折叠表观协同性的来源、形成局部超二级结构的序列模式在决定整体空间结构中的作用等进行分析

和实验探索。

关键字:蛋白质设计,计算方法


91

6 月 17 日上午分会场报告 a（8:30-10:10）

Genetically-encoded Voltage Indicators Based on Electrochromic FRET

邹鹏

北京大学

摘要

Genetically encoded fluorescent reporters of membrane potential promise to reveal aspects of neural function not

detectable by other means. We present a palette of multicoloured brightly fluorescent genetically encoded voltage

indicators with sensitivities from 8–13% ΔF/F per 100mV, and half-maximal response times from 4–7 ms. A

fluorescent protein is fused to an archaerhodopsin-derived voltage sensor. Voltage-induced shifts in the absorption

spectrum of the rhodopsin lead to voltage-dependent nonradiative quenching of the appended fluorescent protein.

Through a library screen, we identify linkers and fluorescent protein combinations that report neuronal action

potentials in cultured rat hippocampal neurons with a single-trial signal-to-noise ratio from 7 to 9 in a 1 kHz

imaging bandwidth at modest illumination intensity. The freedom to choose a voltage indicator from an array of

colours facilitates multicolour voltage imaging, as well as combination with other optical reporters and optogenetic

actuators.

关键字:voltage imaging,fluorescent sensor


92

白细胞细胞骨架动态重组的分子机制及数值模拟

冯世亮 , 章燕 , 龙勉

中国科学院力学研究所



摘要

人体炎症反应发生时，白细胞通过感受其所处环境中化学、力学刺激，利用胞内级联转导通路对所接收信

号进行处理、调控细胞骨架动态重组，进而展现极化、迁移、跨膜转运等一系列行为，并借此到达炎症区

域、行使免疫功能。此前，针对白细胞细胞骨架重组的理论研究多单纯依托图灵、相分离等斑图形成机制，

尚无法全面描述细胞骨架动态重组随时间-空间调控的动力学特性。对此，本文在已有细胞骨架重组信号通

路研究的基础上提出：细胞骨架级联转导通路的构建遵循“多层开关”式内禀策略的新思路，并据此发展了

包含信号接收、信号初步处理、小 G 蛋白动态调控、双向分子输运等模块的数学模型。整体模型由非线性

反应-扩散方程组构成，并通过格子波尔兹曼法（Lattice Boltzmann method，LBM）数值求解。数值模拟结

果显示：信号级联转导通路通过其“多层开关”策略，即：上层模块效应分子均匀或极性分布可调控下层模

块闭合或开启，可最终实现细胞骨架分子（例如：F-actin、Myosin-II）的动态重组。根据建立的模型开展

了白细胞分别接受化学梯度反转信号、均匀信号及快速时变信号刺激时的数值模拟，其结果与已有实验观

测一致。以本文理论模型为基础，今后将进一步发展白细胞细胞骨架重组力学-化学耦合模型，并进行特定

生理环境下白细胞迁移动力学行为的阐述。

关键字:白细胞,细胞骨架,数学模型,数值模拟


93

Super-resolution imaging and reconstructions of chromosome architecture

in yeast and human cell

郝先 , WeberChristian , OuyangWei , ZimmerChristophe

Institut Pasteur

Institut Pasteur

Institut Pasteur

Institut Pasteur

摘要

Chromosomes are arranged non-randomly in the 3D space of cellular nuclei. This architecture is important to key

biological processes including gene expression and DNA repair, but remains poorly understood in detail.

Genome-wide chromosome conformation capture (Hi-C) is currently the most powerful experimental technique to

probe chromosomal structures. However, this technique does not directly provide a description of high-resolution

chromosomal configurations in individual cells and remains blind to the dynamics of chromatin in live cells. In

this research, we aim to develop experimental imaging and associated computational approaches to describe the

structures and dynamics of chromosomes at high resolution in individual cells. We performed this by combining

recent single molecule microscopy approaches with dedicated computational reconstruction methods, partly based

on polymer physics. We then used these approaches to study the changes of chromosome configurations and

analyze their relationship to gene expression and repair of DNA double strand breaks. This research shows

generate new technologies and new fundamental knowledge in the areas of nuclear architecture and function.

关键字:super-resolution imaging,chromosome architecture,computational reconstruction,genome organization


94

Single-Molecule Study Reveals Reactive Oxygen Species mediate BIN2's

activity in Brassinosteroids Signaling Pathway

谭砚文

Fudan University

摘要

Single-molecule fluorescent spectroscopy can provide unique perspectives which complement conventional bulk

biochemical approaches. To illuminate the transmission of signals inside cells, we studied the signaling pathway of

a plant hormone, Brassinosteroids (BRs). BRs are the plant hormones that involved in numerous plant

development processes such as leaf expansion, shoot elongation and pollen tube formation. Once the signal

transduction is initiated by the membrane receptor kinase, the downstream signaling pathway is realized by three

proteins: BIN2 (brassinosteroid insensitive 2), BES1 (BRI1 ems suppressor1) and a kind of 14-3-3s protein. BRs

signaling pathway have been extensively studied via genetics, proteomics, genomics and cell biology techniques.

However, these bulk methods can’t follow the transduction process in situ or resolve molecular details at a rate

matching the true signaling time-scale. Here we use a single molecular assay based on Total-Internally Reflected

Fluorescence (TIRF) microscopy to observe the interaction of these three proteins. The result shows that BIN2 can

phosphorylate BES1 on the order of seconds, and the dimeric 14-3-3s can only bind with BES1 in its

phosphorylated form. In addition, we have, for the first time, found that the interaction between BIN2 and BES1 is

oxygen dependent. This result may have implications on BRs signaling pathway’s involvement of stress

acclimation in plants.

关键字:single-molecule,signalling protein


95

6 月 17 日上午分会场报告 b（8:30-10:10）

Visualizing protein excited-state structures with conjoint use of biophysical

techniques

唐淳

中科院武汉物数所

摘要

A protein can dynamically inter-convert between the predominant ground-state and lowly populated excited-state

structures. The dynamic fluctuation among different conformational states enables the protein to perform its

function. Paramagnetic NMR utilizes a paramagnetic probe specifically conjugated at the protein under

investigation, and provides information about protein structure and dynamics. Among the paramagnetic NMR

techniques, paramagnetic relaxation enhancement (PRE) exhibits an distance dependence and is exquisitely

sensitive to protein minor conformation. In my presentation, I will show how paramagnetic NMR was used to

depict the ensemble structure of noncovalent ubiquitin dimer, and to visualize the quaternary rearrangement of

Lys63-linked poly-ubiquitin. The various quaternary structures allow the poly-ubiquitin to specifically recognize

its target proteins. In conjunction with small X-ray angle scattering (SAXS), cross-linking coupled with mass

spectrometry (CXMS), and single-molecule FRET (smFRET), I will also present our new approach for precise

depiction of protein ensemble structures.

关键字:NMR,Protein Dynamics,Ensemble Structure,SAXS


96

真核七次跨膜蛋白 Leptosphaeria rhodopsin 结构和机理的固体核磁共

振研究

王申林， LiuJing , LiuChang

Peking University

Peking University

Peking University

摘要

Leptosphaeria rhodopsin(LR)是源于真核微生物 L. maculans 的光敏感七次跨膜蛋白,是第一个被发现的源于

真核生物的光驱动质子泵。其功能是在光照条件下跨膜运输氢离子，而 LR 的三维结构以及详尽的质子泵

机理至今仍未阐明。此论文将介绍我们利用固体核磁共振技术研究 LR 结构-功能机理的最新进展。通过多

维多核魔角旋转固体核磁共振实验，完成了大部分氨基酸残基的主链和侧链原子的化学位移指认，以及二

级结构分析（图 1）。结果显示，LR 具有七个跨膜螺旋结构，并且 LR 蛋白的膜外 loop 区有较大柔性。 LR

质子泵发挥功能的关键位点包括：1）LR 蛋白中的视黄醛配体与最后一个跨膜螺旋上的赖氨酸形成的质子

化席夫碱基（SB），以及 2）位于第三个跨膜螺旋的 Asp 150 和 Asp 139 是。选择性 Asp 侧链羧酸基团实

验表明， Asp 150 羧基侧链是质子化的，而 Asp 139 为非质子化的。这两个 Asp 位于膜蛋白的内部，说明

存在稳定的氢键网络或盐桥结构。水-蛋白相互作用实验和 H/D 交换实验则表明处于蛋白内部的席夫碱的质

子和溶剂水存在快速交换，说明质子泵通道内部存在结合水。以上实验现象说明膜蛋白中的结合水以及氢

键网络对 LR 质子泵功能与机理有重要作用。

关键字:固体核磁共振,七次跨膜蛋白,光驱动质子泵,结合水


97

水通道蛋白 AqpZ 结构及功能的固体 NMR 研究

赵永祥


摘要

大肠杆菌水通道蛋白（AquaporinZ, AqpZ）以功能四聚体形式定位在细胞内膜上，能够高效选择性的驱动

水分子的转运，而不让其他小分子或者离子通过，对于维持细胞渗透压平衡具有重要意义[1]。据文献报道，

AqpZ Arg-189,Phe-43 和 His-174 等残基在通道内形成一个选择性滤过区域[2]，通过分子模拟发现 Arg-189

的侧链可以通过上下摆动形成“开”和“关”两种构象[3]，尽管已有 AqpZ 晶体结构报道这种现象[4]，但是

AqpZ 在真实磷脂环境中详细分子转运机制，目前仍然不够清楚。魔角旋转固体核磁共振(Magic-angle

Spinning Solid-state NMR, MAS ssNMR)技术是在磷脂环境中研究膜蛋白结构及动力学行为的有效手段之一，

我们通过 MAS ssNMR 技术对磷脂环境中的 AqpZ 的二级结构以及起门控作用的 Arg-189 侧链构象行为进

行研究；我们首先制备了具有功能活性的 AqpZ 脂质体样品（如图 a 所示），通过 NCACX,NCOCX,CONCA

等三维实验完成 AqpZ 蛋白 93%以上的残基化学位移归属（如图 b，c 所示），并与天然提取含 AqpZ 的细

胞内膜比对发现 NCA 谱图中大部分谱峰能够重叠（如图 d 所示）。通过 AqpZ 脂质体中残基化学位移预测

的二级结构和晶体结构的二级结构进行比对[4]，发现在膜外部分有明显差别（如图 e 所示）。AqpZ 中有 5

个谱峰化学位移很接近的 Arg 残基，为了便于区分 Arg-189 的谱峰，我们将其余 4 个 Arg 都突变成 Lys。

功能实验证明 AqpZ 突变体脂质体仍然具有功能活性（如图 a 所示），通过 13C-15N TEDOR 实验我们观测

到 Arg-189 的侧链只有一套峰（如图 f 所示）。利用量子化学计算方法计算晶体结构中“开”“关”两种构象状

态 Arg-189 侧链原子的化学位移发现，如果存在两种构象，则在谱图中有两套峰，由此我们推断在磷脂环

境中 AqpZ 的 Arg-189 侧链只有一种构象或快速交换的两种构象，这与晶体结构中同时存在“开”和“关”构象

有所区别[5]。综上所述磷脂膜环境对于维持膜蛋白 AqpZ 的结构和功能具有重要意义。

关键字:水通道蛋白 AqpZ,MAS ssNMR


98

基于钻石探针的单分子磁共振波谱新技术

石发展

USTC

摘要

Magnetic resonance (MR) is one of the most important techniques for characterizing compositions, structure and

dynamics of these kind of materials. However, current methods need billions of uniform units on centimeter-scale

to accumulate large enough signal-to-noise ratio. High sensitivity MR techniques are urgently needed for new

applications on nanoscale. A sensor to accomplish nanoscale targets detection is the recently developed atomic

sized magnetic field sensor based on the nitrogen-vacancy (NV) defect center in diamond. By combining the

quantum controls and long coherence time of NV, we have experimentally realized nanoscale nuclear MR and

electron spin resonance. In detail, we firstly realized detection of (5nm)3 hydrogen nuclear spin sample including a

few thousand atomic nuclei under ambient conditions, which is “a first step toward imaging complex molecular

structures directly”. Then we chose a nuclei dimer 13C-13C as a target and realized atomic-scale structure analysis

of the dimer by measuring its coupling vector. Further, nuclear magnetic resoance spectroscopy with single spin

sensitivity was accomplished. Recently, we have realized nanoscale microwave field imaging and even detection

of single protein electron spin resonance spectroscopy. We not only recorded the single-protein magnetic

resonance spectroscopy, but also inferred the motions of the protein by analysis the shape of spectra. These results,

together with the relation works in the field, open a door to nanoscale MR and will be potentially used as a new

tool on smart materials.

关键字:single molecule,magnetic resonance


99

6 月 17 日上午分会场报告 c（8:30-10:10）

A Microfluidic Device Integrating Size Based Separation and Affinity

Capturing for Synergistic Enrichment of Circulating Tumor Cells

杨朝勇

厦门大学

摘要

Circulating Tumor Cells (CTCs) have been demonstrated to be excellent biomarkers for cancer diagnosis and

prognosis. During the past ten years, tremendous amounts of effort have been invested in developing various

microfluidic platforms based on different separation principles ranging from sized/deformity oriented techniques

to immunocapture methods for CTC enrichment. Unfortunately, most of these platforms are often limited by a

capture performance tradeoff between high efficiency and high purity. Towards solving such inherent interest of

attaining high throughput, capture efficiency and purity, we have designed a hybrid microfluidic device for the

enrichment of CTCs relying on both size-based separation and affinity capturing principles. Our computationally

optimized and aptamer functionalized micropillars array chip allows separation of target cells from non-target cells

based on size while facilitating cell-micropillars collision hence highly efficient immunocapturing of CTCs. In this

talk, the design, optimization, and performance of the integrated device will be discussed.


100

二维纳米芯片模板上DNA级联机器模拟分子水平信号传导及其应用

柳华杰

中国科学院上海应用物理研究所

摘要

信号传导是生命体的重要生理功能，是细胞受到外界信号刺激而产生反应的过程，在生命体中发挥了重要

的作用。受此生命过程启发，我们通过 DNA 分子构建了能够响应外界信号，并产生级联运动的纳米机器

系统，对信号传导进行分子水平上的模拟，并探索其在人工生物计算方面的应用。具有纳米可寻址性的 DNA

折纸术结构被选择作为 DNA 级联机器的模板，在外界信号 DNA 作用下，基于 HCR 反应的 DNA 机器实现

了沿预设路径的级联运动，将信息向下级节点传递。通过该设计，我们成功实现了基于多机器的并行计算，

并以迷宫问题为例进行了展示；另一方面，DNA 级联运动机器从原理上避免了 DNA 计算中存在的输入与

输出不一致性问题，首次构建了输入与输出均为同一 DNA 的逻辑门系统；最后，我们以生物检测为例展

示了该体系的潜在应用前景。

关键字:DNA 纳米机器,信号传导


101

基于细胞分群计数的白细胞荧光染色平衡研究

高婷娟

华中师范大学

摘要

床旁诊断（POCT）的大趋势下便携式血细胞计数成为一个急待突破的领域。应对智能、廉价、微创等终极

目标的过程中，流式细胞术和库尔特原理对开发便携式血细胞计数显示了其技术的局限性。鉴于此种现状，

我们开发了一套“血细胞大视场显微成像计数”光学系统，运用单个荧光标记对血样染色，同时记录明场与

荧光成像，并采用计算机程序对成像进行分析。这套仪器与方法可以准确的计算红细胞、血小板、白细胞

及其三分类和血红蛋白的数目，但目前还不能区分白细胞中极微量的嗜酸性粒细胞和嗜碱性粒细胞。因此

我们研究了单个荧光染料吖啶橙对白细胞染色的化学平衡热力学，并提出相应可能的机制。通过此项工作，

白细胞三分类的分群计数得到了理论支持；而且，这种思路将为解决白细胞五分类的挑战提供更有效的研

究方法。

关键字:床旁诊断,便携式显微成像,血细胞计数,成像分析


102

分子伴侣辅助的膜蛋白折叠研究

黄方

中国

摘要

根据 Anfinsen 的研究，蛋白质的序列决定蛋白质的三维结构，这是蛋白质折叠的基本原理。但是越来越多

的研究表明，许多水溶性球蛋白的正确折叠需要分子伴侣的辅助。对于膜蛋白的折叠，虽然一个较为普遍

的观点认为 Translocon 对于膜蛋白的折叠和转运起到关键作用，但是我们对膜蛋白折叠机理的认识还非常

有限。通过对新生膜蛋白折叠速率和折叠后生物活性的研究，我们发现在表明活性剂存在下，所研究的膜

蛋白（CCR5 和 CXCR4）能够自发折叠，但是分子伴侣的存在能够明显的加速折叠过程并提高膜蛋白的生

物活性。这表明，分子伴侣对膜蛋白的折叠也具有辅助作用，在细胞中分子伴侣很可能也参与了膜蛋白的

折叠过程。通过动力学和热力学的研究，我们正努力揭示分子伴侣辅助膜蛋白折叠的分子机制。

关键字:蛋白质折叠,分子伴侣,膜蛋白


103

6 月 17 日上午主会场报告（10:30-11:10）

高效靶向端粒酶和淀粉样蛋白及其作用机制的新进展

曲晓刚

中国科学院长春应用化学研究所稀土资源利用国家重点实验室/化学生物学实验室长春，130022

E-mail: [email protected]

摘要

衰老和与衰老密切相关的疾病如端粒酶相关的癌症以及阿尔兹海默症、帕金森综合症等受到世界各国的普

遍关注并取得重要进展，已成为国内外生命科学和化学领域十分活跃的研究课题。本文主要总结我们近期

在端粒及其复合物功能调节、阿尔茨海默症(AD)抑制剂筛选以及构建药物可控释放等方面取得的一些进展

1-12。感谢科技部 973 重大研究计划及国家自然科学基金委对本研究工作的大力支持。

参考文献

[1] H. Sun, J. Ren, X. Qu, Accounts Chem. Res., 2016, 49, 461-470.

[2] J. Wang, C. Zhao, A. Zhao, M. Li, J. Ren, X. Qu, J. Am. Chem. Soc., 2015, 137, 1213-1219.

[3] F. Pu, L. Wu, X. Ran, J. Ren, X. Qu, Angew. Chem. Int. Ed., 2015, 54, 892-896.

[4] L. Wu, X. Qu, Chem. Soc. Rev., 2015, 44, 2963-2997.

[5] N. Gao, H. Sun, K. Dong, J. Ren, T. Duan, C. Xu, X. Qu, Nature Commun., 2014, 5, 3422.

[6] Y. Lin, J. Ren, X. Qu, Accounts Chem. Res., 2014, 47, 1097-1105.

[7] W. Li, J. Wang, J. Ren, X. Qu, J. Am. Chem. Soc., 2014, 136, 2248-2251.

[8] M. Li, S. E. Howson, K. Dong, N. Gao, J. Ren, P. Scott, X. Qu, J. Am. Chem. Soc., 2014, 136, 11655-11663.

[9] C. Zhao, L. Wu, J. Ren, Y. Xu, X. Qu, J. Am. Chem. Soc., 2013, 135, 18786-18789.

[10] W. Li, J. Wang, J. Ren, X. Qu, Angew. Chem. Int. Ed., 2013, 52, 6726-6730.

[11] Y. Chen, K. Qu, C. Zhao, L. Wu, J. Ren, J. Wang, X. Qu, Nature Commun., 2012, 3, 1074.

[12] J. Geng, M. Li, E. J. Ren, Wang, X. Qu, Angew. Chem. Int. Ed., 2011, 50, 4184-4188.

mailto:[email protected]


104

墙报摘要（按照墙报提交先后顺序）

红外光谱的检测灵敏度和选择性研究进展及其在生物体系中的应用

张文凯 , MarkiewiczBeatrice , RodgersJeffrey , 陈建新 , 盖锋

北京师范大学





摘要

红外光谱已被广泛应用于各种多肽和蛋白质的结构和动力学的研究中。但在推广到生物大分子体系的研究

时却面临着很多困难，主要原因是目前红外光谱的选择性不够好和灵敏度不够高。因此，在多数情况下人

们无法通过生物分子自带的振动模式来获得位点选择的蛋白质结构和动力学信息。为了解决这些困难，我

们发展了非天然氨基酸红外光谱探针并把它们结合到蛋白质中去进行位点选择的光谱研究，我们也发展了

提高二维红外光谱检测灵敏度的实验方法。在此基础上，我们对一些蛋白质体系展开了研究工作。例如，

我们研究了甲型流感病毒中的离子通道 M2，它是由低 pH 激活的质子选择性离子通道，它的质子传导是甲

型流感病毒复制的关键步骤，同时也是抗病毒药物的主要目标对象。过去的研究认为甲型流感病毒 M2 离

子通道内的质子传导的调控是依赖于通道中的水的结构变化。前人的研究表明通道中的 Trp41 氨基酸残基

是负责通道开启和关闭的阀门，我们利用 TrpCN 红外探针研究了不同 pH 值情况下通道中的水的结构和动

力学变化。研究结果表明，Trp41 氨基酸残基附近的水的结构在通道开启和关闭的情况下没有显著的变化。

关键字:红外光谱探针,二维红外光谱,离子通道


105

Nanoparticle-Biomembrane Interactions Investigated by In Situ Surface

Nonlinear Spectroscopy

陆洲


摘要

The interactions between nanoparticles and biological membranes play critical roles in the toxicity and biomedical

functions of nanomaterials. However, there is still a lack of the molecular-level understandings of how the

biological membrane structures respond to the nanoparticle attachments. In this presentation, we will demonstrate

the recent progresses in the in situ characterization of nanoparticle-bimembrane interactions using the sum

frequency generation vibrational spectroscopy (SFG-VS), a surface-selective nonlinear optical probe with the

submonolayer sensitivity. The molecular orientations and interfacial assembly structures of several typical

phospholipid Langmuir monolayers influenced by the hematite nanoparticles will be discussed in detail. Assisted

with the atomic force microscopy measurements, we discovered the hematite nanoparticles prefer to being attached

to the loosely packed phospholipid domains at the air/water interface. The quantitative analysis of the

polarization-dependent SFG-VS results revealed that with the presence of the nanoparticles at the lipid surfaces,

the phospholipid assembly becomes much more tightly packed. These results clearly show that the sum frequency

generation vibrational spectroscopy is fully capable of exploring the nanoparticle-biomembrane interactions in the

aqueous environments.

关键字:生物膜界面,纳米颗粒,表面非线性光学


106

基于超分子自组装原理的“杀菌开关”

白昊天 , 王树



摘要

因缺乏创新的杀菌策略而产生的耐药性问题，已成为 21 世纪人类最重要的公共健康威胁之一。在近期的工

作中，我们设计并成功实现了一种基于超分子自组装原理的“杀菌开关”，提供了一个调控杀菌药物活性的

全新概念。这个“杀菌开关”的实现是基于带有季铵盐侧链的共轭聚合物 PPV 和 CB[7]在组装和解组装状态

下拥有与细菌完全不同的相互作用机制。构建这种简单有效的“杀菌开关”，并不需要对杀菌分子活性位点

进行特殊的化学修饰，同时还可实现对其光毒性的有效调控。从长远来看，这种超分子“杀菌开关”不仅可

成功抵御细菌感染，且有望延缓杀菌分子耐药性的产生。

关键字:共轭聚合物,杀菌开关,耐药性


107

Synthesis of a Novel Quinoline Skeleton Introduced Cationic Polyfluorene

Derivative for Multimodal Antimicrobial Application

孙含

Institute of Chemistry, Chinese Academy of Sciences

摘要

A new functional polyfluorene derivative containing quinoline skeleton and quarternary ammonium groups (QAGs)

modified side chains (PFPQ) was synthesized and characterized. The multimodal antimicrobial effect toward

Gram-negative E. coli. was achieved by the dark toxicity resulting from quinoline skeleton, and QAGs and light

toxicity resulting from reactive oxygen species (ROS) produced by the main backbone of PFPQ under white light.

The mechanism of interaction between PFPQ and bacteria was also demonstrated. PFPQ binded to E.coli mainly

through electrostatic interactions causing nearly 50% bacterial death in the absence of light irradiation, and the

huge capability of PFPQ to generate ROS under white light opens another bactericidal mode. The killing

efficiency was more than 99% upon relatively mild irradiation under white light (400–800 nm) with a light dose of

18 Jcm−2. PFPQ with the incorporation of quinolone into the backbones will provide a new versatile strategy to

achieve the multimodal antimicrobial effect to fight against resistant bacteria.

关键字:polyfluorene,quinoline,ROS,antimicrobial activity


108

基于水溶性共轭聚合物的病原菌检测、杀伤以及抗菌敏感性的评价及

抗生素的筛选研究

王耀坤


摘要

近年来，病原菌感染所引发的公共卫生安全问题引起了人们越来越多的关注。细菌和真菌感染通常会导致

极其严重的后果，甚至会威胁人的生命。与此同时，抗生素的大量不合理使用导致细菌耐药性问题越来越

严重。耐药菌的出现对人类公共安全提出了严峻的挑战，同时也是科研工作者面临的一大难题。传统的病

原菌检测方法大多依赖于病原菌的生长，需要 24-48 h 甚至更长的培养时间，这与病原菌快速检测的需求相

差甚远。因此，发展快速区分检测病原菌、快速评价抗菌药物的敏感性和筛选抗生素的方法以及发展新的

杀菌体系用以解决细菌的耐药性问题具有重要意义。基于以上考虑，我们课题组利用阳离子聚合物之间以

及阳离子聚合物与荧光素之间的荧光共振能量转移（FRET），设计发展了基于阳离子聚合物的病原菌检测

体系，实现了病原菌的快速可视区分和抗生素的高通量筛选。此外，我们设计合成了侧链修饰了胍基的寡

聚芴，利用其与绿色荧光蛋白能发生有效的能量转移建立了一种特异性筛选破膜抗生素的方法。

关键字:抗生素筛选,水溶性共轭聚合物,共振能量转移


109

疏水单元对 i-motif DNA 二级结构稳定性的研究

孙亚伟，徐海

China University of Petroleum

China University of Petroleum

摘要

i-motif 是一类富含 C 碱基的 DNA 在弱酸性或中性条件下形成的四链二级结构。我们考察了疏水单元的引

入对单分子、双分子及四分子 i-motif 结构稳定性的影响，通过测量 i-motif 的解离温度来研究其稳定性。

我们设计并合成了一系列以 i-motif DNA 作为亲水片段的两亲脂核酸，发现单分子 i-motif 的热稳定性几乎

不受疏水单元的影响，而双分子及四分子 i-motif 的热稳定性可随疏水单元的引入增加，其中四分子的 i-motif

的熔点温度升高十分明显。这表明疏水单元的引入对促进核酸二级结构的形成与稳定有较大贡献，该研究

为在温和条件下调控核酸构型具有重要意义。

关键字:i-motif,热稳定性,脂核酸


110

一种改进的副本交换方法

陈长军

华中科技大学物理学院

摘要

会务组老师，你好，如果可能的话，我希望能有机会做口头报告，谢谢。作为一种分子模拟中的优秀算法，

副本交换方法一直得到了广泛的应用，它的采样效率和计算时间由预先设定的温度数目和副本数目决定，

二者密切关联。在本工作中，我们对传统的副本交换方法做了改进，各个温度上的副本被分为活跃副本和

非活跃副本。活跃副本在恒定温度上做常规动力学采样，而非活跃副本则从预先设定的状态数据库中采样。

事实上，该方法完全消除了副本数目和温度数目的内在关联，因此，我们可以在分子模拟中按照需要自由

设置温度和副本。实际计算结果表明，改进后的副本交换方法比传统方法表现更好，在同等计算量的条件

下，它可以提供更为准确的采样数据，包括自由能和热熔等等，这对分子模拟有着重要意义。

关键字:副本交换方法,分子模拟


111

自驱动胶体马达：可控分子组装，理论模拟及生物医学应用

贺强 , 志光吴 , 司铁岩 , 林显坤





摘要

自驱动胶体马达：可控分子组装，理论模拟及生物医学应用吴志光，司铁岩，林显坤，贺强* 哈尔滨工业

大学微纳米技术研究中心，150080，哈尔滨 * E-mail: [email protected] 自驱动胶体马达是近十年来国际

科学研究的热点领域之一。通过模拟自然界中活性生物马达的结构和功能，经由化学合成或可控组装的方

法，将化学能或其它形式的能量转换成机械能从而实现合成胶体粒子或组装体的运动功能，最终完成在微

纳米尺度上的运动。目前大多数相关研究集中在阴阳实心微球、金属合金微管及金属纳米线马达，这些合

成马达虽然实现了在溶液中的自驱动，但其本身不具有负载功能，并且与生物体系的相容性较差，在实际

应用中具有很大的局限性。我们课题组在过去五年中运用从下到上的可控分子自组装结合从下到上的制造

方法，选用不同的有机分子、高分子或生物大分子、纳米粒子等构筑单元，制备了从几个微米到几十个纳

米的一维、二维或三维胶体马达。这些不同尺寸和结构的胶体马达可以在不同化学催化反应或光、超声等

外场驱动下发生自驱动运动，结合流体力学和计算机模拟方法分析了胶体马达的个体运动机理和群体运动

行为，特别是在强布朗运动存在下的运动行为研究。因为经由可控分子组装制备的自驱动胶体马达具有多

功能化的优点，我们也考察了自驱动胶体马达在生物医学领域如药物运输、血液毒素清除、辅助伤口愈合、

生物分子分离和纯化等方面的应用可能。参考文献： [1] X. Lin, Z. Wu, Y. Wu, M. Xuan, Q. He, Adv. Mater.,

2016, 28, 1060-1072. [2] Z. Wu, T. Si, W. Gao, X. Lin, J. Wang, Q. He, Small, 2016, 12, 577-582. [3] J. Shao, M.

Xuan, L. Dai, T. Si, J. Li, Q. He, Angew. Chem. Int. Ed., 2015, 54, 12782-12787 [4] Z. Wu, X. Lin, Y. Wu, T. Si,

J. Sun, Q. He, ACS Nano, 2014, 8, 6097-6105. [5] Z. Wu, Y. Wu, W. He, X. Lin, J. Sun, Q. He, Angew. Chem. Int.

Ed. 2013, 52, 7000. [6] Y. Wu, Z. Wu, X. Lin, Q. He, J. Li, ACS Nano, 2012, 6, 10910.

关键字:胶体马达,自驱动,可控分子组装,群体行为,生物医学应用


112

阳离子 OPV 用于光拮抗细胞耐药性研究

周鑫 , 吕凤婷 , 刘礼兵 , 王树

中科院化学所

中科院化学所

中科院化学所

中科院化学所

摘要

在肿瘤治疗中，化疗是一种广泛使用的治疗方式。然而，细胞耐药性的产生严重影响了肿瘤的治疗和预后，

已成为全球科研和医疗人员需要面对的严峻问题。在复杂的耐药机制中，外排蛋白造成的药物外排是其中

最常见的肿瘤耐药机制。人们发展了几种策略来克服药物外排引起的细胞耐药，但是疗效不能让人满意而

且具有很高的毒性，因此很难应用于临床治疗。光操作作为一种非侵入性的远程时空可控的手段，被广泛

用于生命活动研究以及疾病治疗。由于可远程操控和低毒性的优点，光操作在癌症治疗和解决耐药性方面

也非常有潜力。我们组设计了一种新的基于光操作来拮抗肿瘤细胞的耐药性的策略。我们引入了一个可嵌

插入细胞膜的阳离子寡聚 OPV。在光照下，该 OPV 可以敏化产生活性氧，改变细胞膜的通透性。抗肿瘤

药物发生急速内在化并增加在耐药细胞中含量，最终实现对耐药细胞药物毒性的恢复。最后我们通过量热

法分析发现光敏剂与药物分子的相互作用对药物的内在化有促进作用。

关键字:OPV,光拮抗,耐药性


113

3-羟基黄酮类 Zn2+荧光探针的设计、合成及其在前列腺癌细胞识别

上的应用

徐玉林 , 李节 , 刘长林




摘要

前列腺癌是男性常见的恶性肿瘤，死亡率紧随肺癌之后位居第二。目前被广泛应用于前列腺癌早期诊断的

前列腺特异性抗原检测在敏感性和特异性两方面均不够理想。游离的 Zn2+作为前列腺癌候选标志物的研究

已有半个世纪，在发生癌变过程中，前列腺细胞里 Zn2+的浓度随着锌转运蛋白的表达下调而明显降低。因

此，发展高亲和性游离 Zn2+探针有助于发展新的前列腺癌诊断试剂。目前所报道的具有荧光背景低、灵敏

度高、选择性好、细胞渗透性好以及在细胞中停留时间长的 Zn2+荧光探针仍然较少。本文设计及合成了

Zn2+荧光探针 3HC-DPA，并通过荧光实验证实 3HC-DPA 在溶液中与 Zn2+结合具有很好的灵敏度和较高

的选择性。而且 3HC-DPA 在哺乳动物活细胞中具有较好的细胞渗透性和较长的细胞停留时间，其中，激

光共聚焦和流式细胞术实验结果显示，通过内源性 Zn2+或者外加 Zn2+成像，3HC-DPA 可以区分前列腺正

常细胞和癌细胞。

关键字:Zn2+荧光探针,前列腺癌,3-羟基黄酮


114

共轭聚合物—纳米银复合体系在无标记蛋白检测中的应用

王晓瑜 , 李盛亮 , 张鹏博 , 王树





摘要

随着基因组学与蛋白组学的蓬勃发展，研究工作者不断发现与疾病相关的新型生物标志物。而肿瘤标志物

如抗原作为一种诊断工具在诊断、预测和监测癌症中扮演十分重要的角色。基于抗体—抗原相互作用实现

抗原的特异性识别将可以更好地对疾病进行早期干预和治疗。由于荧光检测具有高灵敏度和高效率特性，

已经被广泛用于医学诊断，生物分子间相互作用识别和细胞成像等领域。因此，将抗体—抗原相互作用转

换为荧光信号的变化将可以成为抗原检测的有效手段之一。金属增强荧光效应具有距离依赖性。在该研究

中，我们基于银纳米结构的金属增强荧光效应，构建了共轭聚合物 PFVCN—银三棱柱的光学复合体系用于

蛋白的无标记检测。首先，在石英基底吸附银纳米粒子后组装聚乙烯亚胺/聚丙烯酸多层膜，通过聚丙烯酸

的羧基将人前列腺特异性抗原抗体 anti-PSA 引入该体系。利用抗体—抗原相互作用使表面的荧光共轭聚合

物 PFVCN 与底部的银纳米结构之间距离发生变化，从而调控金属增强荧光效应，获得共轭聚合物荧光信

号的改变。该体系成功将人前列腺特异性抗原 PSA 的捕获引起的距离变化转变为荧光信号的量变，可以用

于特异性抗原的高效、灵敏检测。在此基础上，我们偶联上皮细胞粘附分子抗体 anti-EpCAM 于该基底上，

实现了不同肿瘤细胞的捕获与检测。

关键字:共轭聚合物,蛋白检测


115

Cationic Conjugated Polymers-Induced Quorum Sensing of Bacteria Cells

张鹏博


摘要

Bacteria quorum sensing (QS) has attracted significant interest for understanding cell−cell communication and

regulating biological functions. In this work, we emonstrate that water-soluble cationic conjugated polymers

(PFP-G2) can interact with bacteria to form aggregates through electrostatic interactions. With bacteria coated in

the aggregate, PFP-G2 can induce the bacteria QS system and prolong the time duration of QS signal molecules

(autoinducer-2 (AI-2)) production. The prolonged AI-2 can bind with specific protein and continuously regulate

downstream gene expression. Consequently, the bacteria show a higher survival rate against antibiotics, resulting

in decreased antimicrobial susceptibility. Also, AI-2 induced by PFP-G2 can stimulate 55.54 ± 12.03% more

biofilm in E. coli. This method can be used to understand cell−cell communication and regulate biological

functions, such as the production of signaling molecules, antibiotics, other microbial metabolites, and even

virulence.

关键字:bacteira,quorum sensing


116

聚合物纳米粒子的制备及其细胞膜成像研究

贺萍 , 李梦 , 刘礼兵 , 吕凤婷 , 王树






摘要

相比于游离的聚合物，聚合物纳米粒子具有许多独特的优点，如荧光亮度高、光稳定性好、细胞毒性低及

表面修饰简易等，因此，聚合物纳米粒子在细胞成像方面具有很大的应用前景。由于细胞的内吞作用，能

稳定定位在细胞膜表面上的纳米粒子鲜有报道，而特异性的细胞膜定位染料对于细胞形态和结构的研究至

关重要。本研究工作中，我们制备得到了药物 Plerixafor 修饰的纳米粒子 PFPNP-PLE。对该纳米粒子进行

DLS 以及 SEM 表征，发现 PFPNP-N3 的粒径大约为 136 nm，zeta电位为-27 mV，PFPNP-PLE 的粒径在 176nm

左右，zeta 电位为 7.2 mV，粒径和 zeta 电位的结果都证实了药物分子 Plerixafor 连接到了纳米粒子的表面。

光稳定性测试表明，我们制备的聚合物纳米粒子具有很好的光稳定性。细胞毒性结果表明，PFPNP-PLE 对

HeLa，HT-29 和 MCF-7 三种细胞系均没有明显的细胞毒性，表明了其良好的细胞相容性。最后，我们利用

该聚合物纳米粒子进行细胞成像研究，并用商业化的细胞膜染料进行共定位，结果表明，PFPNP-PLE 可以

定位在细胞膜上。

关键字:共轭聚合物,纳米粒子,细胞膜成像,Plerixafor


117

A Fluorescence Ratiometric Assay Strategy for Chemical Transmitter of

Living Cells Using H2O2 – Sensitive Conjugated Polymers

王云侠


摘要

A new water-soluble conjugated poly(fluorene-co-phenylene) derivative (PFP-FB) modified with

boronate-protected fluorescein (peroxyfluor-1) via PEG linker has been designed and synthesized. In presence of

H2O2, the peroxyfluor-1 group can transform into green fluorescent fluorescein by deprotecting the boronate

protecting groups. In this case, upon selective excitation of PFP-FB backbone at 380 nm, efficient fluorescence

resonance energy transfer (FRET) from PFP-FB backbone to fluorescein occurs, and accordingly, the fluorescence

color of PFP-FB changes from blue to green. Furthermore, the emission color of PFP-FB and the FRET ratio

change in a concentration-dependent manner. By taking advantage of PFP-FB, ratiometric detection of choline and

acetylcholine (ACh) through cascade enzymatic reactions, and further dynamic monitor of choline consumption

process of cancer cells have been successfully realized. Thus, this new polymer probe promotes the development

of enzymatic biosensors and provides a simpler and more effective way for detecting chemical transmitter of living

cells.

关键字:water-soluble conjugated polymers,FRET,detection,chemical transmitter,living cells


118

模拟细胞膜体系制备及应用

韩晓军


摘要

细胞膜行使信号转导、物质转运等重要生理功能。模拟细胞膜体系为细胞膜的简化模型。从细胞膜的基本

成分 - 磷脂分子出发，可构建平板磷脂双层膜体系和球状磷脂囊泡体系。这些体系可用于研究细胞膜的生

物物理性质及其生理功能。这里将重点介绍场诱导的磷脂膜组装体系，包括磷脂囊泡和磷脂管，1-3 以及

它们在作为模板材料、药物控释以及原细胞等领域的应用。

关键字:磷脂囊泡,原细胞


119

姜黄素与 CopC 相互作用的光谱研究

宋珍，lubaoping ，杨斌盛

太原师范学院化学系

太原师范学院

山西大学

摘要

ApoCopC 是由 102 个氨基酸残基组成的铜伴侣蛋白。核磁结构显示该蛋白质在溶液中是由 9 股 β 折叠

片形成的希腊桶状结构。ApoCopC 特有的结构特点使得其具有容纳小分子的性质。姜黄素是一种 β -二酮

类中药有效成分，具有抗炎、抗癌、免疫调节、凋亡调节以及鳌合金属离子等方面的复合特性。本文通过

荧光光谱、紫外吸收光谱及分子模拟研究了姜黄素与铜离子以及铜伴侣蛋白 CopC 的相互作用。结果表明：

姜黄素可以与铜伴侣蛋白 CopC 形成 1:1 的复合物，结合常数为 7.8×105 M-1。根据在不同温度下的热力

学参数 ΔH0，ΔS0 和 ΔG0 的大小，可以判断出 CopC 与姜黄素结合的主要作用力为疏水作用力。

关键字:姜黄素,CopC,Cu2+


120

具有活性氧自清除能力的聚噻吩在细胞成像中的应用

陈艳艳 , 胡蓉 , 吕凤婷 , 刘礼兵 , 王树






摘要

荧光材料因为其高灵敏度及多样性在基础研究及疾病诊断中得到了广泛的应用。有机小分子染料和量子点

是目前应用比较广泛的两种荧光材料，但这两种材料面临着光漂白严重及重金属带来的细胞毒性等问题。

共轭聚合物相比于这两种材料具有强的光捕获及信号放大能力并应用于生物、化学传感器中，除此之外，

共轭聚合物还具有高的量子产率及高的光稳定性等优点，使其在细胞成像中具有很好的应用前景。在此基

础上，我们设计并合成了侧链带有季氨盐及叠氮基团的聚噻吩，通过 click 反应在聚噻吩的侧链修饰上二氢

吡啶，利用药物分子能够消耗活性氧，实现了高光稳定性及低光毒性的细胞成像，使体系具备良好的生物

兼容性。

关键字:共轭聚合物,活性氧自清除,细胞成像


121

聚噻吩-DNA 杂化水凝胶的制备及细胞捕获、杀伤研究

卢欢


摘要

水凝胶，尤其是 DNA 水凝胶，由于其多样性以及良好的生物相容性得到了越来越多的关注。制备水凝胶

的方式趋于多样化，包括交联反应、酶催化交联、原位聚合、自由基聚合和离子反应，这为凝胶的应用打

下夯实的基础。凝胶目前主要应用于化学、材料以及生物医学领域，除了能很好的捕获负载蛋白、DNA 和

药物分子外，通过修饰水凝胶还实现了病毒的检测以及捕获。尽管做了很多努力，但集成像、细胞捕获以

及杀伤的多功能水凝胶鲜少报道。这里我们利用钆离子与羧基以及磷酸根之间的螯合作用，以鲑鱼精 DNA、

侧链修饰有羧基的聚噻吩 PT-COOH 与钆离子制备成了具有成像、细胞捕获以及杀伤的 DNA 水凝胶。除此

以外，该凝胶制备方法快速、简单。这不仅丰富了 DNA 水凝胶的功能，也拓展了其在生物医学领域的应

用

关键字:阳离子共轭聚合物,水凝胶,DNA,自组装,细胞捕获


122

pH 值响应的共轭聚合物纳米粒子的制备、表征与细胞成像研究

王建武


摘要

共轭聚合物纳米粒子（CPNs）因其高荧光亮度、低毒性、表面易修饰的特性，近年来在生物材料和生物医

药领域备受关注。本论文中我们设计、合成了一种新的 pH 值响应共轭聚合物（PFPA），并通过纳米沉淀

方法制备了其纳米粒子。动态光散射实验表明 PFPA 纳米粒子在水中分散性较好，其粒径约为 8 nm。PFPA

纳米粒子的最大吸收峰为 379 nm，其摩尔吸光系数为 2.1×106L•mol-1•cm-1；另外该纳米粒子的荧光最大发

射峰为 422 nm，其荧光量子产率为 35%。PFPA 纳米粒子载汞灯（100 瓦）照射下表现出较好的光稳定性，

另外 MTT 实验表明其具有较低的细胞毒性。该纳米粒子具有 pH 响应的光学特性，并可以用于活细胞成像。

PFPA 纳米粒子在癌症诊断、药物与基因传递等方面具有潜在的应用价值。

关键字:共轭聚合物纳米粒子,荧光探针,pH 响应性


123

基于氧化石墨烯/共轭聚合物复合材料的蛋白检测和功能调控研究

邢成芬 , 范一冰 , 柴燃

河北工业大学

河北工业大学

河北工业大学

摘要

将共轭聚合物和氧化石墨烯（GO）进行优势互补形成复合荧光探针将大大提高荧光探针与生物分子的相互

作用及信息表达。而且，在利用非共价方式构建复合荧光探针的过程中，GO 和共轭聚合物的结构不被破

坏，其自身的性质得以保留。因此，共轭聚合物/GO 复合荧光探针可以提高共轭聚合物和 GO 纳米材料

的可操控性，拓展其在生物化学传感领域的应用。我们提出将共轭聚合物/GO 复合荧光探针与钙调蛋白的

特异性检测及功能调控有机结合起来，发展了基于共轭聚合物的蛋白质检测体系。利用阳离子聚噻吩与钙

调蛋白的静电和疏水相互作用构建自组装体系，通过钙离子诱导的蛋白构象变化调控聚噻吩的构象变化，

导致聚噻吩产生变色效应，发展了一种简单、定量、肉眼可视的检测钙调蛋白的新检测体系。并且，可以

通过钙离子调控蛋白与共轭聚合物的组装过程。在此基础上，最近，通过钙离子诱导的钙调蛋白构象变化

调控与 GO 的组装，进而利用不同的组装体在空间上控制与共轭聚合物的荧光共振能量转移（FRET）效率

进行蛋白检测，发展了简单、肉眼可视、信噪比高的钙调蛋白传感体系。

关键字:共轭聚合物,氧化石墨烯,蛋白检测,功能调控


124

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein

Reveals the Mechanism for Ribonucleoprotein Complex Formation

王文明 , 郭宇

山西大学

南开大学

摘要

Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including

humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome

(HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the

genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal

structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV),

which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV

NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic

study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding

extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in

RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region

connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through

contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs

extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP.

This work provides insight into the formation of hantavirus RNP and provides an understanding of the

evolutionary connections that exist among bunyaviruses.

关键字:Hantavirus Nucleocapsid Protein,Crystal structure


125

Conjugated Polythiophene for Rapid, Simple and High-Throughput

Screening of Antimicrobial Photosensitizers

牛瑞民 , 邢成芬 , 李瑞华

河北工业大学生物物理所



摘要

Photodynamic antimicrobial chemotherapy (PACT) is effective for the treatment of pathogenic infections. Here,

we present a platform for high-throughput screening of PACT photosensitizers based on a cationic conjugated

poly[3-(3′-N,N,N-triethylamino-1′-proryloxy)-4-methyl-2,5-thiophene hydrochloride] (PMNT). The PMNT can be

simply used to quantitatively measure the amounts of bacteria in high sensitivity only via various fluorescence

quenching efficiencies in the presence of bacteria. The photosensitized inactivation of bacteria is not efficient with

ineffective photosensitizers (PS), and thus the bacteria grow exponentially and can be coated tightly by PMNT

through electrostatic and hydrophobic interactions, resulting in the formation of aggregates and the fluorescence

quenching of PMNT. In the presence of effective PS, the bacteria can be efficiently killed in PACT and the PMNT

fluorescence is not obviously affected, leading to original and strong fluorescence of PMNT. This new platform of

high-throughput screening is promising for discovering new PS.

关键字:biosensor,conjugated polymers,fluorescence,high-throughput screening,photosensitizer


126

水溶性石墨烯量子点的合成与表征

高天，刘义

武汉大学

武汉大学

摘要

量子点是准零维纳米材料，其特殊的光学性质使得它在生物医学和光电材料等研究领域中具有很大的应用

前景。相较于传统的半导体量子点，石墨烯量子点具有低毒性和良好的水溶性，因此在生物医学上有更好

的应用前景。此外，通过特定的表面修饰，能增强石墨烯量子点的生物相容性，并改变其光学性能。本文

以炭黑作为原材料，采用自上而下的方法，利用酸解与超声，合成出粒径分布窄、单分散性良好、生物相

容性优良、低毒性、抗光漂白的新型石墨烯量子点，并进行了系列表征与生物毒性测试。

关键字:石墨烯量子点,纳米材料,发光材料


127

银原子簇对大肠杆菌抗菌活性的研究

金建成 , 吴小娟 , 王贝贝 , 蒋风雷 , 刘义






摘要

银材料作为抗菌剂的应用，已有上千年的历史。近年来，纳米银成为了生物医学领域应用中新一代的纳米

产品，对它抗菌机制的研究也成为一个热点。超小粒径的贵金属纳米团簇是介于分子与纳米颗粒之间的桥

梁，它们的能级是不连续的，有着类似分子的性质。由于它们优异的物理、化学性质，它们在生物标记、

生物成像、催化和纳米电子学等方面被广泛的应用。然而，作为银材料特性的抗菌性，银原子簇的这一性

质还研究的很少。本文在温室下合成了二氢硫辛酸保护的银原子簇，研究了它对人胃粘膜上皮细胞的活性

的影响，发现银原子簇对人胃粘膜上皮细胞没有明显的毒副作用，说明银原子簇有着良好的生物相容性。

紧接着，我们研究了银原子簇对大肠杆菌的抗菌活性，结果显示在 15 mg/L 时银原子簇即可完全抑制大肠

杆菌的生长，表明银原子簇有着作为对人体无毒却有优异抗菌性能的抗菌剂的巨大潜力。

关键字:银原子簇,生物相容性,抗菌


128

Photosynthesis Controlled Detection of Carbon Dioxide Base on

Guanidinium Pendant Oligofluorene

邢成芬 , 袁宏博 , 范一冰

河北工业大学生物物理研究所



摘要

A strategy combines water-soluble conjugated oligofluorene tethered guanidinium groups (OF) with anionic

polythiophene derivative (PTP) for sensing carbon dioxide (CO2) has been demonstrated. The superquenching

property of OF by PTP and the specific character of guanidinium groups response to CO2, make the technique

detect CO2 selectively and sensitively. Intriguingly, the concentration changes of CO2 controlled by

photosynthesis have been illustrated as well. Moreover, this strategy is a fluorescent, visible and “turn on”

approach. Therefore, the technique provides a promising application in detection of CO2 and presents a concept to

regulate the photosynthesis in a confined space base on water-soluble conjugated polymers.

关键字:carbon dioxide (CO2),conjugated oligofluorene,guanidinium group,photosynthesis,stimuli-responsive


129

Location, Function and Structural Dynamics of a Vibrational Marker in a

Photoactive Protein

王建平，于鹏云，杨帆




摘要

Upon the binding of a ruthenium carbonyl complex to photoactive yellow protein, large conformation of the

protein was observed. Steady-state and time-resolved spectroscopic methods, in particular ultrafast 2D IR

spectroscopy, were applied to characterize the location, function and structural dynamics of the vibrational marker

and its interaction with the protein.

关键字:Vibrational marker,Protein structural dynamics ,2D IR,Photoactive yellow protein,Structural intermediate


130

NO、O2 铁卟啉键合产物研究进展—晶体结构与化学键振动

李剑峰

中国科学院大学

摘要

Oriented single-crystal nuclear resonance vibrational spectroscopy (NRVS) has been used to obtain all iron

vibrations in two {FeNO}6 porphyrinate complexes, five-coordinate [Fe(OEP)(NO)]ClO4 and sixcoordinate

[Fe(OEP)(2-MeHIm)(NO)]ClO4. Single crystals of both complexes were oriented to be either parallel or

perpendicular to the porphyrin plane and/or axial imidazole ligand plane. Thus, the FeNO bending and stretching

modes can be unambiguously assigned. DFT calculations were also used to obtain detailed predictions of

vibrational modes. Predictions were consistent with the intensity and character found in the experimental spectra.

The NRVS data allow the assignment and observation of the challenging to obtain Fe−Im stretch in six-coordinate

heme derivatives. NRVS data for this and related six-coordinate hemes with the diatomic ligands CO, NO, and O2

reveal a strong correlation between the Fe−Im stretch and Fe−NIm bond distance that is detailed for the first time.

The synthesis and X-ray structural characterization of the first, five-coordinate {FeNO}8 porphyrin structure

[Co(CP)2]+[Fe(TFPPBr8)NO]- and the five-coordinate nitrosyl precursor [Fe(TFPPBr8)NO] are reported. The

comparison of the two 100 K structures suggests significant differences on the axial Fe–NO bond distances and the

Fe–N–O angles. The slightly shorter average Fe–Np bond distance of [Fe(TFPPBr8)NO]- is consistent with the

DFT predictions and the singlet state of the iron center. Mossbauer measurements confirmed the low-spin state of

the two complexes. IR and UV-vis spectra are also reported.

关键字:porphyrin,iron,NO,O2


131

石墨烯量子点的离子响应

王晞 , 高天 , 巴晓旭 , 刘义

武汉大学

武汉大学

武汉大学

武汉大学

摘要

由于石墨烯量子点(GQDs)具有因为量子限域效应和边界效应而带来的一系列新的特性，引起了化学、物理、

材料和生物等各领域科学家的广泛关注 1,2。此外，石墨烯量子点较于传统量子点的低毒性、良好的水溶性

及生物相容性等优势,使其在生物医学上有更广阔的前景。其中，利用石墨烯量子点对金属离子的响应,来进

行生物成像和生物传感,是其在生物医学方面的重要应用之一。本文以炭黑为原料，利用自上而下的方法，

合成了石墨烯量子点，并进行了其对不同金属离子的响应的探究。

关键字:石墨烯量子点,纳米发光材料,离子响应


132

用于胞内 GSH 检测的水溶性“off-on”荧光探针性能研究

黄蓉

武汉大学

摘要

谷胱甘肽(GSH)，是由谷氨酸、半胱氨酸和甘氨酸组成的一种天然活性肽，存在于所有的动物细胞中，在

基因表达调控、细胞保护、氨基酸转运、免疫功能调节等许多生命活动中起着直接或间接的作用[1]。此外，

研究表明细胞溶血症、糖尿病、动脉粥样硬化、炎症、帕金森症及部分神经类疾病也都与体内 GSH 的水平

异常有关[2]。因此，GSH 的检测具有重要意义。目前，检测 GSH 的荧光探针大都存在着一些缺陷：如不

能特异性将 GSH 与其他天然巯基化合物如半胱氨酸(Cys)、同型半胱氨酸(Hcy)分开；水溶性差；灵敏度低；

反应时间长；毒性较大。所以，设计合成高效的 GSH 探针仍然具有挑战性。在课题组相关工作基础上[3]，

本文以罗丹明 B (RhB)为荧光基团，以 α,β-不饱和 C-C 双键为反应基团，合成了系列化学反应型荧光探针。

其中，RhB-1 具有良好的水溶性，能够在水体系下进行光学检测，表现出荧光开关行为(off-on)，并且能进

行了细胞成像。激光共聚焦显微成像表明 RhB-1 能够很好进入细胞，在胞内 GSH 作用下显示荧光信号。

通过对该系列探针进行构效关系研究，获得影响探针性能的关键因素。该研究对巯基探针的理性设计和进

一步发展具有重要意义。

关键字:GSH,荧光探针


133

等温滴定量热在蛋白纤维化研究中的应用

杨琪琦 , 张嘉淇 , 刘义




摘要

人胰岛素蛋白(insulin)在一定的条件下能够聚集发生纤维化，例如：II 型糖尿病人长期局部注射胰岛素来调

节体内血糖平衡，这有可能造成胰岛素的局部浓度过高引起的聚集，最终产生纤维化。研究结果表明：人

胰岛素蛋白发生纤维化存在着典型的迟滞效应，即‘成核’阶段，这说明蛋白单体要形成成熟纤维需要跨越

一定的能垒，才能进行之后指数增长达到最终的平衡。硫黄素 T (ThT)被广泛用于研究蛋白聚集过程，是一

类检测具有 β-sheet 结构的荧光染料，利用 ThT 可以对人胰岛素蛋白纤维化过程进行动力学研究。圆二色谱

(CD)广泛用于检测蛋白质二级结构，结合荧光光谱，说明随着纤维化过程的进行，蛋白单体二级结构逐渐

解螺旋，由最初的 208 nm 以及 222nm 处的 α-helix 特征峰逐渐消失，β-sheet 含量逐渐增大。对蛋白纤维化

的详细过程及其机理，还有待于进一步研究。

关键字:蛋白纤维化,硫黄素 T,圆二色谱


134

In vitro effect of nicotine on isolated mitochondria studied by

spectroscopic and microscopic methods

LiuJun-Yi , ZhangYue ,马龙，蒋风雷

University High School of Indiana, Carmel, IN 46032, United States

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China



摘要

Nicotine is widely considered as a main cause for many chronic diseases and lung cancers. We have investigated

the effect of nicotine on the function of mitochondria isolated from rat livers by spectroscopic and microscopic

methods. The influence of nicotine on mitochondrial respiration, swelling, membrane potential and lipid

peroxidation was evaluated. We observed that nicotine could directly affect the mitochondrial membrane

properties and induce lipid peroxidation. Notably, nicotine showed a protective effect on Ca2+-induced

mitochondrial permeability transition. The results will help us learn more about the biological effect of nicotine at

subcellular (mitochondrial) level and propose a way to understand the role of nicotine on Parkinson’s disease.

关键字:mitochondria,nicotine


135

Development of a Refined Benchmark for Assessing Scoring Functions Used

in Protein-Protein Docking

韩莉，刘志海，李嫣，李婕，王任小

State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,

Chinese Academy of Sciences









摘要

Scoring functions are dispensable for the success of protein-protein docking methods. They need to be evaluated

on some high-quality benchmarks to recognize their strength and weakness. Current benchmarks for evaluating

protein-protein docking protocols have certain limitations for this purpose. We thus aimed at establishing a new

refined benchmark particularly for evaluating protein-protein scoring functions. Our benchmark, namely

CASF-PPI-2015, is based on a non-redundant set of 273 protein-protein complexes. These complexes were

selected through a systematic sampling of the entire Protein Data Bank. Experimentally measured binding data of

these complexes were all curated from original references. A series of quality-control checks were conducted in

selection of these complexes to ensure that their structures and binding data do not have obvious problems. By our

evaluation methods, the performance of a scoring function is measured in two basic aspects, i.e. "docking power"

and "scoring power". Four composite scoring functions, including ATTRACT, dDFIRE, FASTCONTACT and

ZRANK, were tested on our benchmark as examples. ATTRACT and ZRANK exhibited promising performance

in the docking power test. However, all four scoring functions failed badly in the scoring power test. Our

benchmark is freely available to the public. We hope that it will become a valuable community resource.

关键字:Protein-protein interaction,Scoring function,Protein-protein benchmark


136

有机胂化合物引起线粒体 Ca2+依赖的膜渗透性转换孔的开放

樊晓阳 , 刘玉娇 , 刘义

武汉大学

武汉大学

武汉大学

摘要

自 As2O3 被成功用于治疗急性早幼粒细胞白血病之后，关于砷化合物的研究越来越多[1]。相较于无机砷而

言，有机胂因其结构多样性和良好的生物活性，得到了较多关注。本文合成了一种有机胂化合物 PDT-PAO，

并探究其在细胞层面和亚细胞层面的生物活性，发现它对多种癌细胞具有较好的杀伤效果，尤其是白血病

细胞 NB4 和 HL-60，其 IC50 分别为 1.25 ± 0.02 µM 和 1.12 ± 0.02 µM。通过对线粒体功能的检测，我们发

现 PDT-PAO 会影响线粒体，并且引起线粒体膜电势坍塌和膜肿胀，发生 Ca2+依赖的 MPTP 开放，并最终

导致细胞色素 c 的释放和细胞凋亡。

关键字:有机胂,线粒体,MPTP,细胞凋亡


137

荧光金纳米团簇与蛋白质相互作用的热力学基础

尹苗苗

武汉大学

摘要

荧光金纳米团簇由几个到几十个金原子组成，粒径一般约 1-2 nm，介于金原子(atom)和金纳米粒子

(nanoparticle)之间，是一类重要的荧光纳米材料，具有超小尺寸和良好生物相容性等优点。蛋白质是生物体

的重要组成物质之一，对众多生命现象起着至关重要的作用，是生命科学研究的重要对象。当金纳米团簇

进入生命体系，首先会遇到各类蛋白质，并与之相互作用。这些作用均可能导致蛋白质的结构和功能发生

变化，也对金纳米团簇的理化性质和行为特征产生重要影响。因此，阐明金纳米团簇与蛋白质相互作用的

热力学基础具有重要意义。本文制备了粒径约为 1.7 nm 的荧光金纳米团簇[1]，采用微量热、荧光光谱、紫

外-可见吸收光谱、圆二色谱等技术和方法[2]，研究了金纳米团簇与血清白蛋白、γ-球蛋白、转铁蛋白等丰

度较高蛋白质的相互作用，初步阐明了其相互作用机制。

关键字:金纳米团簇,蛋白


138

靶向天然无序蛋白的理性药物设计

阮浩 , 余辰 , 来鲁华

北京大学

北京大学

北京大学

摘要

天然无序蛋白是一类在生理条件下没有固定二级或三级结构的蛋白质。真核生物的天然无序蛋白含量比原

核生物更高。相比于有序蛋白，无序蛋白在功能上有独特特点，在生物网络中常处于枢纽位置。生物信息

学预测发现，与信号转导、癌症、心血管疾病、神经退行性疾病等相关的蛋白有 52%-67%的蛋白是天然无

序蛋白。无序蛋白结构的异质性，为传统基于结构的理性药物设计带来了很大挑战。我们在前期工作中针

对原癌基因 c-Myc 无序结构域开展了构象分析[1]与抑制剂设计，获得了多个活性化合物[2]。综合分析活性

分子与多种构象的结合特征，我们提出了无序蛋白质药物设计的“多构象亲和”策略。目前正在使用这一策

略进行靶向抑癌基因 p53 N 端无序区的药物设计研究。p53 N 端的转录激活区与蛋白 MDM2，MDMX 的相

互作用是阻止野生型 p53 发挥抑癌功能的决定性因素。我们期望通过靶向 p53 N 端无序区，阻止 p53 与

MDM2、MDMX 相互作用，进而激活 p53 通路。已利用全原子分子动力学模拟，得到 p531-39 的构象系综，

并通过聚类得到其代表性构象。使用本组开发的 CAVITY 程序预测了蛋白构象中的可药口袋，最终选择八

个口袋开展化合物分子对接虚拟筛选。挑选能与多个构象结合的分子进行体外活性表征，相关实验正在进

行中。

关键字:天然无序蛋白,c-Myc,p53,药物设计


139

Probing Conformational and Electronic Changes in Redox Proteins with

Electrochemical Surface Plasmon Resonance

Dr. TJ Jing

Biosensing Instrument Inc.

摘要

Redox reactions in proteins and other molecules are known to cause conformational changes in the proteins.

Understanding these changes in proteins and other biomolecules is important because of their critical roles in many

biological functions and processes. However, these changes are often small and fast, making it difficult to measure

and monitor by structural analysis techniques. Surface plasmon resonance (SPR) spectroscopy is a phenomenon

that occurs when polarized light hits a metal film at the interface of media with different refractive indices. This is

a label-free and powerful technique that has been widely used for studying small biomolecule kinetic processes.

Recently, Electrochemical enhanced Surface Plasmon Resonance (EC-SPR) has been utilized to successfully

detect small conformational changes in surface bound molecules. In this presentation, the electron-transfer reaction

in the Horse heart Cytochrome c is measured with EC-SPR technique. The study shows that the electron transfer

reaction-induced conformational changes in Cytc involve a slow collective structural relaxation rather than simply

a local change in the axial ligands. The conformational changes following an oxidation are slower than those

following the reduction of Cytc, which agrees with an earlier circular dichroism study. Other EC-SPR applications

such as studies of small molecule-protein interactions, determination of toxins in food analysis, and a new method

of exploring in situ effects of carcinoma cells treated with potential drugs will also be covered in this presentation.

关键字 :Surface Plasmon Resonance,Electrochemistry SPR,Protein conformational changes,Small molecule

kinetics


140

胆固醇在生物膜中的传输与组装的和频光谱研究

郁婷 , 叶树集



摘要

胆固醇是脊椎动物细胞膜的重要组成物质，对于维持细胞的正常生理功能非常重要。胆固醇分子在人体内

的不正常分布会导致很多疾病，比如动脉硬化和其他心脑血管疾病。理解胆固醇分子在细胞膜中的传输行

为对于理解这些疾病的发病机理至关重要。本研究中，我们利用和频振动光谱技术（SFG-VS）系统研究了

胆固醇分子在不同种类的磷脂双层膜中的运输和组装行为。结果表明，胆固醇在磷脂双层膜中是否翻转主

要取决于磷脂是否翻转，磷脂分子和胆固醇分子的动力学行为是同步的。在电中性的磷脂膜中，胆固醇非

常快地从双层膜的一侧翻转到另一侧，而电中性的磷脂分子和胆固醇具有一样的动力学曲线和翻转速率。

但是，当把磷脂换成带负电的磷脂时，胆固醇不发生或只发生一部分翻转，这主要是因为带负电的磷脂与

基体材料有很强的相互作用，因此负电荷磷脂不发生翻转，而这也恰好说明了胆固醇的在生物膜中的翻转

主要取决于磷脂是否发生翻转。

关键字:胆固醇,翻转（Filp-flop）


141

F16 类有机胂化合物对细胞凋亡的探究

刘玉娇


摘要

本文通过探究 F16 类的有机胂化合物 PDT-PAO-F16 对人急性早幼粒白血病细胞 NB4 的增殖和凋亡方面的

影响，发现该化合物能够显著抑制 NB4 细胞的增殖，其 IC50 为 0.67±0.14µM，而该化合物抑制 NB4 细胞

增殖的主要途径是通过引发线粒体功能损伤从而引发细胞凋亡。这有助于阐述有机胂化合物的抗癌活性机

理。

关键字:F16,有机胂,细胞凋亡


142

量热法测量氯已定对白色念珠菌生长代谢的影响

徐娟 , 刘义 , 蒋风雷




摘要

氯己定化学名称为 1,6-双(正-对氯苯双胍)己烷。氯己定是一种阳离子型化合物，对细菌有很强的亲和力，

能损伤细菌细胞膜，以及抑制细菌代谢酶活性，从而能抑制细菌生长。本文通过量热法研究氯已定了对 C.

albicans 生长代谢的影响，从热谱图中可以看出氯已定对 C. albicans 的生长代谢有很强的的抑制作用，随着

氯已定浓度增加，出峰时间延后，最大产热峰峰值降低。根据热谱曲线，可以得到白色念珠菌在不同浓度

氯已定作用下的生长速率常数。对生长代谢热谱图进行分析，还可以进一步得到一系列的参数和实验结果。

关键字:氯已定,白色念珠菌,量热


143

Computational Design of Fibrous Proteins

许菲

Jiangnan University

摘要

As the most abundant protein in human, collagen serves as a scaffold of biological processes in extracellular

connective matrix. Collagen has also been widely utilized as bioactive cell culture substrates in tissue engineering.

Here, I approach biophysical properties of collagen in two aspects (1) computational design of collagen sequences

to induce the orthogonal assembly of multiple heterotrimers via electrostatic interactions[1, 2]; (2) computational

modeling of collagen inter-helical interactions via shape complementarity to promote its higher-order assembly [3].

With these projects, we demonstrate how computational methods could help to design collagen-based biomaterials.

关键字:collagen ,computational design


144

不同配体修饰 CdTe 量子点对线粒体渗透转换孔的影响

向迅 , 蒋风雷



摘要

量子点由于其优良的光电性质，近年来在生物标记、成像、电子器件等方面得到了广泛的应用。随着其应

用的增多，有必要对其潜在的生物毒性做更多的了解。有研究表明，线粒体是量子点毒性的靶向细胞器之

一，量子点可以损伤线粒体的形态及功能。本文以巯基丙酸(MPA)和巯基乙酸(TGA)为配体，采用水相合成

法，合成了 2 种粒径相近的 CdTe 量子点，并研究比较了 2 种量子点对线粒体渗透转换孔(MPTP)的影响。

结果表明，2 种量子点都可以诱导 MPTP 的开放，但 MPA 修饰的 CdTe 量子点比 TGA 修饰的 CdTe 量子点

对 MPTP 的影响更大。我们对这 2 种量子点引起 MPTP 开放的机理进行了研究，并探讨了这 2 种量子点影

响 MPTP 能力差异的原因。

关键字:量子点,不同配体,MPTP


145

三种亲脂性阳离子线粒体靶向性能研究

高涛 , 向讯 , 蒋风雷 , 刘义

武汉大学

武汉大学

武汉大学

武汉大学

摘要

以荧光染料 BODIPY 为母体，通过柔性碳链分别连接三乙胺、三苯基膦及 F16，合成得到了三种线粒体靶

向荧光探针。通过 MTT、Confocal、FL 及流式细胞仪等方法检测，对比了其荧光量子产率、细胞毒性、线

粒体定位能力、细胞摄取速率等。发现三种靶向基团所对应的荧光探针其细胞毒性较低，线粒体定位能力

都较好，其中三乙胺探针的荧光量子产率最高，水溶性最好，细胞摄取速率最快。因此，三乙胺盐有潜力

取代三苯基膦盐成为优秀的线粒体靶向基团。

关键字:线粒体靶向,亲脂性阳离子,荧光探针,BODIPY


146

Temperature effect on the dynamics of fluorescence probe for specific

detection of cysteine

王芳芳，蒋风雷，刘义




摘要

Biological thiols play pivotal roles in human physiology, such as cysteine (Cys), homocysteine (Hcy) and

glutathione (GSH), design and synthesed the hight selectivity and specififity fluorescent molecular probes for

selective detection of thiols of have attracted much attention. Specifically, Cys is a precursor of GSH, acetyl Co-A

and taurine, as well as a source of sulfide in iron–sulfur clusters. Many human diseases are caused by abnormal

levels of Cys. We have synthesized red-emitting (580nm) molecular probe based on a styryl boron-dipyrromethene

(BODIPY) /2,4-di -nitrobenzenesulfonyl (DNBS) dyad for specific detection of cysteine among the biological

thiols. Adding Cys basically before and after does not have Stokes shift. The results showed that the thiol probe

has excellent specificity toward cysteine over other biologically related thiols, such as glutathione. To study about

the effect of different temperature on the dynamics of reactiong rate, shows that the reaction rate vary with rising

temperature, and at 29°C, the reaction rate is the slowest, correspond with the types of REDOX reaction.

关键字:cysteine,DNBS,kinetics


147

pH-induced conformational isomerization of colicin A pore forming domain

黄艳 , 樊俊鹏 , LakeyJeremy , 刘义

武汉大学

武汉大学

University of Newcastle upon Tyne

武汉大学

摘要

Colicin A is a bacterial toxin which kills colicin-sensitive bacteria by forming a voltage-gated channel in the

cytoplasmic membrane. The pore forming domain of colicin A (ColA-P) is consisting of two hydrophobic helices

and eight tightly surrounded amphipathic helices. It requires acidic phospholipids in the target inner membrane to

enables it to form an insertion competent state and penetrate the membrane during the voltage-gate formation

process. Earlier studies have shown that ColA-p adopt a range of conformational changes depending on the pH of

the solution in vitro. In this study we have characterized the near and far UV CD spectra of ColA-P at different pH.

And the results show that the pH dependent molten globule state can be formed at pH 3.0 in vitro. The absence of

thermal transitions of ColA-P detected by DSC at pH 3.0 also indicate that the protein need less energy to

transform from its molten globule state to its unfolded stage. However, the intrinsic fluorescence spectra shown

that the tryptophan residues of ColA-P are less exposure to the hydrophilic environment at low pH. This result

means that the helix rotates during its molten globule state formation process and the tryptophan residues turn to

the hydrophobic interface at low pH. However, the near UV CD spectra shows that the protein loses its tertiary

structure at low pH. Thus, I conjectured that parts of the surrounded helices extend away from the hydrophobic

core and some of the helices, such as the helices contain tryptophan residues shrink towards the hydrophobic core

at low pH.

关键字:ColA-P,insertion competent state,molten globule state,pH dependent


148

界面蛋白质-蛋白质与蛋白质-磷脂相互作用的非线性光谱识别

张柏雄 , 叶树集 , 罗毅

合肥微尺度物质科学国家实验室



摘要

生物界面上蛋白质-蛋白质以及蛋白质-磷脂之间的相互作用直接决定蛋白质在生物膜上的结构、功能和宏

观性质。但是分子间的相互作用是一种远程的、强度较弱的相互作用，在实验上很难直接测量出来，一般

只能从研究体系的谱学和物化特性等的变化中间接得到或通过探测动态分子能量转移来获得。理论上，激

发态分子之间的相互作用与特定功能团的光谱峰宽直接相关，蛋白质与蛋白质之间的相互作用越强酰胺 I

峰宽越宽。根据此概念，我们以纯 α-螺旋结构的蛋白质 WALP23 为模型，发展新方法来精确测量界面蛋白

质酰胺 I 谱带峰宽，建立了蛋白质-蛋白质、蛋白质-磷脂相互作用与蛋白质酰胺 I 谱带峰宽之间的对应关系。

结果表明，WALP23 与流动性磷脂 POPG 双层膜作用时，酰胺 I 谱带峰宽为 5-7 cm-1，以蛋白质-磷脂相互

作用为主。但在常温下，WALP23 与凝胶相磷脂 DPPG 双层膜作用时，由于 WALP23 蛋白质在磷脂表面聚

集，蛋白质与蛋白质之间的作用较强，此时，酰胺 I 峰宽增加到 17 cm-1；通过加热把 DPPG 变成流动相，

WALP23 蛋白质插入到磷脂 DPPG 双分子层内，结果蛋白质与磷脂之间的相互作用增强，酰胺 I 峰宽减小

到 12 cm-1。该研究表明了蛋白质酰胺 I 信号的峰宽可作为一种区分蛋白质与蛋白质以及蛋白质与磷脂之间

的相互作用的探针。

关键字:界面蛋白质,相互作用,酰胺 I 峰宽,和频光谱


149

金属镉离子结合蛋白生物传感器的理性设计

李烆一 , 张长胜 , 来鲁华

北京大学

北京大学

北京大学

摘要

功能性蛋白质是很多重要生物过程的基础，其中金属离子结合蛋白作为功能性蛋白质的一个重要组成部分

在生物体系中发挥着至关重要的作用。理性设计和改造金属离子结合蛋白不仅可以帮助我们认识金属离子

与蛋白质之间的相互作用规律，还可以为重构生物途径提供工具[1-2]。我们在前期工作中针对铀酰离子

UO2+开展结合蛋白设计，基于组里前期针对蛋白质相互作用设计所建立的“蛋白质关键残基嫁接”策略发展

了一种 UO2+结合蛋白质设计方法及程序 URANTEIN，从自然界中已存在的蛋白质骨架中计算筛选出合适

的蛋白质结构并进行设计改造，最终获得与 UO2+结合能力达到飞摩尔量级的蛋白质[4]。目前正在利用类

似策略进行镉(Cd2+)离子结合位点设计。我们期望通过在大肠杆菌内源性核糖结合蛋白（RBP）骨架结构

的基础上进行改造,通过其与镉离子结合后构象的变化引发下游信号，从而可用镉离子控制细菌的趋向性和

相关基因表达。通过首轮计算得到 7 个蛋白质突变体,在细菌水平上筛选发现，表达 Cadb-1 和 Cadb-5 两个

突变体的大肠杆菌在高于正常大肠杆菌 Cd2+致死浓度下可以生长。我们利用等温滴定量热技术（ITC）测

定了这两个突变体与镉离子的结合能力，进一步的实验正在进行中。

关键字:金属结合蛋白,UO2+,Cd2+,蛋白质设计


150

Single-molecule and ensemble FRET reveals the conformational

heterogeneity and allosteric mechanism of human Hsp70

吴思, HongLiu , 杨洁 , YangJie , ZhangHong , PerrettSarah


Tsinghua University





摘要

Hsp70 is a conserved molecular chaperone which plays an indispensable role in regulating protein folding,

oligomerization, and degradation in prokaryotic and eukaryotic organisms. Hsp70 consists of an N-terminal

nucleotide binding domain, a beta-sheet-containing substrate binding domain and an alpha-helical C-terminal lid

domain. It is an ATP-dependent chaperone which hydrolyzes ATP to ADP resulting in inter-domain

conformational changes and cycling between substrate-binding and release states. However, the conformational

dynamics and the ATP hydrolysis-driven conformational cycle is still under exploration. Here, using human Hsp70

as a model, we studied changes in the conformational distribution of Hsp70 in different nucleotide and substrate

binding states by single molecule FRET. The results show that the conformation of its apo and ADP states are

heterogeneous, while its ATP state is uniform. We also studied the kinetics of ATP-induced conformational

changes in real time by ensemble FRET and analyzed the results using a global mathematical model, which reveals

a fast reversible ATP binding process and a slow rate-limiting domain movement process. Furthermore, our single

molecule and ensemble FRET observations explain the dramatic difference in behavior between Hsp70 with or

without a His-tag. The results provide new insight into the allosteric mechanism of Hsp70.

关键字:single molecule detection,FRET,Hsp70,molecular chaperone,allostery


151

生物钟网络小分子调节剂的设计与发现

解晓雯

北京大学

摘要

Circadian clocks are intrinsic, time-tracking systems that enable organisms to anticipate environmental changes

and allow them to adapt their behavior and physiology to the appropriate time of day. Daily behavior that are

asynchronous with the natural light/dark cycle, such as shift work, jet lag and sleep deprivation, which are called

chronobiology disorders, have been strongly and consistently associated with a number of chronic diseases,

including diabetes, heart disease, cancer, obesity and some other metabolism diseases. As a key member of the

core circadian network, Cryptochrome (CRY) directly inhibits the expression of phosphoenolpyruvate carboxylase

(PCK1) and glucose-6-phosphatase (G6PC), two essential molecules involved in the gluconeogenesis program in

the metabolic network. Until now, several molecules are found to regulate circadian network, most of them are

period-lengthening ones. Period-shortening molecules are less common with unclear mechanism. Here, we

identified potential allosteric regulation sites of CRY based on its crystal structure and molecular dynamics

simulations, and used structure-based virtual screen to discover circadian modulators, especially the

period-shortening modulators. Two period-lengthening molecules and four period-shortening molecules were

discovered using the in vitro binding assay and cell phenotypic functional assay. Further functional analysis of

these compounds is under investigation and their influences on metabolic diseases will also be explored in the

future.

关键字:cryptochrome ,circadian clock,metabolism,period modulators


152

Thermodynamic and kinetic observation of transmembrane segments of

CXCR4 binding to GroEL

迟海霞，王小强，李世新，任浩，徐燕，黄方







摘要

The Escherichia coli molecular chaperone GroEL is an important nano-cage for protein folding. Using peptide

substrates as mimetics of non-native proteins in GroEL-assisted folding has the advantage that this approach

circumvents complications through kinetic competition between substrate folding and binding. We previously

found that GroEL can greatly facilitate the folding of a seven-transmembrane protein of C-X-C receptor type 4

(CXCR4). Here the affinity of the transmembrane helices (TM1-TM7) of CXCR4 for chaperonin GroEL was

investigated with isothermal titration calorimetry (ITC) and fluorescence anisotropy. Important binding parameters

including binding number (n), equilibrium dissociation constant (KD), enthalpy (ΔH), entropy (ΔS) and

dissociation rate constant (kd) for each peptide with GroEL were determined, respectively. Meanwhile, we found

that the seven transmembrane peptides competed in binding to GroEL with a strong binding peptide

(SWMTTPWGFLHP), which identified by other group using phage display showed high affinity for the apical

domain of the chaperonin. This suggests that the CXCR4 peptides probably bind to the same region of GroEL with

even higher affinity. Our study is central to understand GroEL-assisted membrane protein folding.

关键字:GroEL,seven-transmembrane helixes,ITC,anisotropy,binding affinity


153

Ultrastructure perturbation of pulmonary surfactant monolayers by inhaled

single-walled carbon nanotubes with defined aspect ratio and surface

pattern: internalization pathways

徐燕，岳同涛，黄方

China University of petroleum



摘要

Single-walled carbon nanotubes (SWCNTs) are widely used in different areas especially the field of biomedicine

as drug vehicles. However, large scale production and various applications of SWCNTs have raised health and

environmental concerns. As the entrance of inhaled nanoparticles, the lung establishes a significant barrier:

pulmonary surfactant monolayer (PSM) to protect the respiratory system. Here, we have applied molecular

dynamics simulations to probe how the shape and surface property of SWCNTs modulate their interaction with

PSM. For pristine SWCNTs, they can insert into or be wrapped by PSM, depending on their aspect ratio. The final

entry angle is determined by competition between speed of tube rotation and that of PSM invagination. For

hydrophilic tubes, they directly translocate across the PSM. The random entry angle determined the perturbation of

PSM. Patterned SWCNTs with stripy modification or random modification regulate frustration of PSM. Lipids

would adjust their configuration spontaneously to accommodate the hydrophobicity mismatch. Comparatively,

patterned SWCNTs with wider stripe may facilitate their translocation with minimized PSM frustration. This work

may answer questions about inhalation toxicity of SWCNTs and the design of functionalized SWCNTs for

biomedical applications.

关键字:single-walled carbon nanotubes,pulmonary surfactant monolayer


154

Molecular Modeling of Interplay between Nanoparticle Wrapping and

Clustering of Inner Anchored Membrane Proteins

李世新，岳同涛，黄方




摘要

The receptor mediated endocytosis of nanoparticles (NPs) is known to be size and shape dependent but regulated

by membrane properties, like tension, rigidity and especially membrane proteins. Compared with transmembrane

receptors which directly bind ligands to provide the driving force for passive endocytosis, the hidden role of inner

anchored membrane proteins (IAMPs), however, has been grossly neglected. Here, by applying the N-varied

dissipative particle dynamics (DPD) techniques, we present the first simulation study on the interplay between

wrapping of NPs and clustering of IAMPs. Our results suggest that the wrapping dynamics of NPs can be

regulated by clustering of IAMPs, but in a competitive way. In the early stage, the dispersed IAMPs rigidifies the

membrane and thus restrains NP wrapping by increasing the membrane bending energy. However, once the

clustering completes, the rigidifying effect is reduced. Interestingly, the clustering of longer IAMPs can sense NP

wrapping. They are found to preferentially locate at the boundary region of NP wrapping. More importantly, a late

membrane monolayer protrusion is initiated by adjacent IAMP clustering and gradually wraps the NP from the top

side. Our findings regarding the competitive effects of IAMP clustering on NP wrapping facilitate the molecular

understanding of endocytosis and establish fundamental principles for design of NPs for widespread biomedical

applications.

关键字:Molecular Modeling,Interplay,Nanoparticle Wrapping , Anchored Membrane Protein


155

Combinational biosynthesis of novel dual-functional phycobiliproteins and

its application in early diagnosis of liver cancer

吝晓君 , 王祥法 , 葛保胜 , 黄方





摘要

The development of fluorescent tools with high fluorescence quality and efficient targeting is of great importance

in immunoassay. Here we report combinational biosynthesis of novel dual-functional phycobiliproteins by fusing

streptavidin with phycobiliproteins, which can covalently carry different phycobilins for fluorescence assay and

also efficiently target for biotinylated substances. After purification, the recombinant dual-functional

phycobiliproteins can achieve a purity over 95%, and the maximum absorption and fluorescence emission

wavelength are at 624nm and 646nm for SA-PCA-PCB, and 556nm and 568nm for SA-PCA-PEB respectively.

The fluorescence quantum yields and biotin binding activities are 0.10 and 2.2u for SA-PCA-PCB, 0.41 and 4.1u

for SA-PCA-PEB respectively. We then evaluate the application of these dual-functional phycobiliproteins in early

diagnosis of liver cancer using “sandwich” ELISA method. As a result, both SA-PCA/PCB and SA-PCA/PEB

show a good liner function with biomarkers (AFP & CEA) of early liver cancer within 0-50 ng/mL concentrations.

Their LODs are 0.25ng and 1.01ng for AFP, and 0.28ng and 1.12ng for CEA using SA-PCA-PEB and

SA-PCA-PCB respectively. The results indicate that these novel dual-functional streptavidin-phycobiliproteins are

useful tools for a wide variety of immunoassay, and may have the advantages in its higher expandability and

compatibility with existing and future immunoassay technologies.

关键字:dual-functional,phycobiliproteins,streptavidin,immunoassay


156

基于多巴胺受体蛋白结构中的分子通道理论透视帕金森病病理

徐四川

云南大学

摘要

多巴胺是脑内一种重要的神经递质，通过不同亚型多巴胺受体调控生命体运动功能、认知活动、情感等生

理或病理过程，与帕金森病(Parkinson’s disease, PD)的病理机制与防治密切相关[1]。在国家自然科学基金支

持下，通过研究多巴胺受体膜蛋白结构与应用[2], 我们建立了《多巴胺分子通道理论》[3-6]。该理论基本

观点是，在多巴胺受体内部有两种分子通道，一种是功能通道，定义为多巴胺分子发挥其功能作用的通道；

另外一种是保护通道，定义为防止过多的多巴胺分子发挥功能作用的通道，起着保护神经系统的作用，称

之为保护分子通道。基于该理论和其它大量的基础研究和动物实验，我们提出帕金森病另外一种发病机制

是神经系统多巴胺功能分子通道被纤维蛋白堵塞，危险因素是高含量的纤维蛋白。根据该病理新机制，神

经元细胞总是可以分为凋亡、变性但还未凋亡和正常细胞。神经元细胞凋亡（例如脑萎缩）确实能引起帕

金森病，但是对于变性细胞和正常细胞，由于被堵塞的功能通道可以被疏通，高水平的纤维蛋白含量可以

被降低，减少的多巴胺可以通过治疗和康复以及外源补充方式得到恢复和提高，所以基于发病新机制，帕

金森病将期望能被控制和治愈。目前，帕金森病被认为是一种不可治愈的致残性疾病，不可治愈性与其病

理被认为是中脑黑质多巴胺能神经元不可逆的进行性凋亡密切相关，因为凋亡的神经元细胞无法被修复。

新旧帕金森病病理是相互包容、相互补充的，当然，相互不冲突，相互不否定，现有病理强调细胞凋亡的

属性，新病理则强调未凋亡细胞的性质和功能。本报告，还将介绍许多实验和观察结果，支持帕金森病发

病新机制，包括大量的动物实验，以及基于发病新机制，在世界上第一次成功治愈一例病龄 14 年志愿患者

的帕金森病。

关键字:帕金森病,病理,分子通道理论,多巴胺受体


157

多态性蛋白 Mad2 折叠与功能的研究

张会亭 , 黄方 , 赵园园




摘要

多态性蛋白 Mad2 折叠与功能的研究摘要：Mad2 是纺锤体检查点（Spindle Assembly Checkpoint, SAC）的

关键蛋白，在有丝分裂过程中能阻止未成熟的姐妹染色单体分离以确保遗传物质均匀地分配到子代细胞中，

从而保证遗传的稳定性。研究发现 SAC 在肿瘤的发生、发展中扮演着重要的角色，已成为肿瘤治疗的重要

靶点。Mad2 有两种不同的天然构象：O-Mad2 和 C-Mad2，且两种构象间可以转变。本文通过热力学和动

力学研究发现这两种构象间存在中间体（Intermediate，I），其中 U 和 O-Mad2 间存在中间体 I1，U 和 C-Mad2

间存在中间体 I2，中间体结构显著减慢了 O-Mad2 和 C-Mad2 构象间的转变。成功构建了 Mad2 的双定点突

变体，用荧光染料 Alexa Fluor 488（AF488）和 Alexa Fluor 647（AF647）对突变体蛋白进行双标记，以构

建 FRET 体系。利用单分子荧光共振能量转移技术（sm-FRET）研究该双标记蛋白的动力学过程。初步研

究发现，在生理状态下，这两种状态会同时存在，并被有效调控。基于这一体系，可以对这两种构象与蛋

白质间的相互作用进行研究。关键词：Mad2，构象转变，折叠中间体，单分子荧光共振能量转移

关键字:Mad2,构象转变,折叠中间体,单分子荧光共振能量转移


158

《Kinetic and thermodynamic studies reveal chemokine homologues

CCL11 and CCL24 fold differently》

孙婷婷，葛保胜，黄方

Center for Bioengineering and Biotechnology, China University of Petroleum (Huadong)



摘要

Proteins with low sequence identity but comparable tertiary structure and functions have been valuable to uncover

the relationship between sequence, tertiary structure, folding mechanism and functions. Two homologous

chemokines, CCL11 and CCL24, with low sequence identity but similar tertiary structure and functions, provide

an excellent model system for respective studies. However, little is known about the folding of these two important

chemoknies with great potential as therapeutic. Here, the kinetics and thermodynamics of the two chemokines,

CCL11 and CCL24, were systematically characterized. Despite of their similar tertiary structure, CCL11 and

CCL24 shows different thermodynamic stability in guanidine hydrochloride solution, with D50=2.20 M and 4.96

M, respectively. The kinetics curves clearly show two phases in the unfolding process of both CCL11 and CCL24,

which suggests the existence of an intermediate state in the unfolding process of the two chemokines. The folding

pathway of both CCL11 and CCL24 could be well described using a folding model with an on-pathway folding

intermediate. However, kinetics and stability of the intermediate state of CCL11 and CCL24 are obviously

different in their folding process. Our results suggest that closely related homologous chemokines can show

distinct thermodynamic stability and folding pathway.

关键字:chemokine,thermodynamics,kinetics,folding intermediate


159

Tracking live cell membrane invagination of the single virion by force

tracing based on atomic force microscopy

单玉萍，王宏达

School of Chemisty and Life Science, Advanced Institute of Materials Science, Changchun University of

Technology

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese

Academy of Sciences

摘要

The first step in most viral infections is the penetration of the cell membrane via endocytosis. However, the

underlying mechanism of this important process has not been quantitatively characterized; for example, the

velocity and force of a single virion during invagination remain unknown. Here, we monitored the endocytosis of a

single live virion through the apical membranes of a host cell by developing and using a novel ultrafast (at the

microsecond level) tracking technique: force tracing. Based on atomic force microscopy (AFM), single-virus

particles were attached onto a highly sensitive AFM tip via a flexible PEG linker; thereafter, the process of viral

invagination was measured by changes in deflection of the AFM tip. This report utilizing high temporospatial

resolution (subnanometer and microsecond levels) approaches provides new insight into the dynamic process of

viral infection via endocytosis and the mechanism of membrane invagination at the single-particle level.

关键字:Force tracing ,atomic force spectroscopy


160

X-ray Crystallography Applied in Nucleotide-Transition Metal Coordination

Complexes

李晖，仇启明

北京理工大学

北京理工大学

摘要

Nucleotides are essential components of DNA and RNA, and their functions depend mainly on the participation of

metal ions. Thus, research into nucleotide–metal coordination complexes, including the affinities of different

coordination donors for metal ions, molecular and crystal structures, supramolecular assembly, and functional

nanoparticles, will contribute to the interdisciplinary field of chemistry, biology, and materials. Comprehensive

analysis on the molecular structures and crystal structures of nucleotide–metal coordination complexes are very

important to understand their properties. X-ray single crystal diffraction is the most powerful method to study the

structures of crystallized materials. At present, the crystal structures about nucleotide–metal complexes are very

limited, which are due to the ambivalent properties of nucleotide molecules, and most metal ions can catalyze the

non-enzymatic hydrolysis of nucleotide phosphate groups. We are interested in research of the crystal structures of

nucleotide–metal complexes based on X-ray single crystal diffraction method. So, we have made great efforts in

preparing single crystals of hybrid compounds of nucleotide with transition metal ions. Then, the coordination

activity of nucleotides, controllable synthetic strategies for nucleotide–metal complexes, and the relationship

between their structures and properties can be studied based on their crystallography. Recently, some interesting

and important results have been obtained, which are ranging from simple complexes to 1D and 2D polymers, as

well as 3D supramolecular assemblies. The functional properties of these nucleotide–metal complexes, such as

their luminescence, magnetism, and adaptive inclusion properties, in particular, the chirality of nucleotide–metal

complex, including their molecular chirality, supramolecular helical chirality, and extended axial chirality have

been summarized.

关键字:Nucleotide,X-ray Crystallography


161

Femtosecond laser-induced nano-explosion for the destruction of

amyloid-beta fibrils with gold nanorods

林冬冬，HeRuoyu , 杨新菊

Fudan University

Fudan University

Fudan University

摘要

Alzheimer’s disease (AD) is associated with the aggregation of the amyloid-beta (Aβ) peptides into toxic

aggregates. How to inhibit the aggregation of Aβ peptides has been extensively studied over recent decades. The

methods for eliminating the formed fibrils, however, have been reported rarely. Here, gold nanorods (Au NRs) are

attempted for the destruction of formed mature Aβ fibrils under the irradiation of near infrared femtosecond (fs)

laser (~800 nm). Our results demonstrate that the fs-laser irradiation can locally trigger the explosion and melting

of Au NRs adsorbed on Aβ fibrils due to the strong localized surface plasmon resonance effect. The majority of

Aβ fibrils are broken to small fragments with 5-minute exposure of fs-laser, while the destruction effect is much

weaker by continue wave laser with equivalent power density and exposure time. Meanwhile, the β-sheet

structures are found to be reduced dramatically. In addition, with pulsed laser irradiation on gold nanoparticles (Au

NPs), most Aβ fibrils keep well but disruption of Au NPs. Compared with the former studies in eliminating

amyloid aggregates, we find a high-efficient method to destruct the amyloid fibrils by fs-laser locally and

bio-compatibly, providing a possible route on therapy of AD.

关键字:gold nanorods,femtosecond laser,Alzheimer’s disease,nano-explosion,fibrils destruction


162

水溶性阳离子共轭聚合物的细胞成像和基因递送研究

李盛亮 , 吕凤婷 , 刘礼兵 , 王树





摘要

基因治疗俨然发展成为当前疾病治疗新模式[1]。基因治疗的核心是基因载体的发展，当前使用的基因载体

主要包括病毒类和非病毒类载体。虽然病毒载体在基因治疗具有转染效率高的特性，但是其潜在的生物安

全隐患极大地阻碍了在临床的应用。非病毒载体，作为新兴的一类生物安全载体，正在被不断开发。聚合

物，作为目前极力发展的载体之一，其本身的低转染效率和高细胞毒仍然限制了它的进一步应用。此外，

目前的聚合物仍缺乏自身荧光特性，不能实时成像基因传递过程和细胞内定位情况。因此，发展新型高效

低毒且具有自发荧光的基因载体仍迫在眉睫。荧光共轭聚合物由于其独特的光电特性，一直倍受科学家们

的亲睐。特别是近些年来，共轭聚合物已经发展成为一种新型的生物传感、生物成像以及抗菌抗肿瘤应用

平台。然而基于共轭聚合物的基因递送研究鲜有报道。因此，我们设计并合成了新型新型水溶性阳离子共

轭聚合物 CCP，该 CCP 具有良好的荧光稳定性和生物安全性，且其本身的荧光为细胞成像提供了有力工具。

CCP 的细胞内 DNA 转染和 GFP 质粒表达效率证实了 CCP 的高转染能力。综上所述，我们基于水溶性阳离

子共轭聚合物 CCP 发展了新型基因转染载体材料[2]。关键词: 共轭聚合物、基因治疗，基因载体、细胞成

像参考文献 [1] Feng X1, Liu L, Wang S, Zhu D, Chem Soc Rev. 2010, 39, 2411-9. [2] Feng X, Lv F, Liu L,

Yang Q, Wang S, Bazan GC, Adv Mater. 2012, 24, 5428-32. 致谢: 本研究得到国家自然科学基金(NO.

21033010，TRR61，21373243)和中国科学院战略性先导科技专项的支持。

关键字:共轭聚合物,基因治疗,基因载体,细胞成像

F


163

转录因子与 DNA 相互作用调控机制的分子动力学模拟研究

高军 , 熊乐 , 李根

华中农业大学信息学院



摘要

在真核生物中，转录因子可特异性结合 DNA 序列，精确调控遗传信息的转录过程，与细胞的代谢、周期、

分化及死亡等各个过程密切相关。转录因子与 DNA 结合过程涉及到蛋白核酸相互作用、蛋白蛋白相互作

用、残基突变及单核酸多态性等诸多因素。目前我们对这些因素组合调控转录因子的特异性结合的分子机

制还知之甚少。我们采用分子动力学模拟方法，并结合生物信息学统计信息，从蛋白蛋白相互作用、单核

酸多态性等方面探讨了转录因子组合调控的分子机制。研究表面，BZIP 家族中转录因子二聚体间因残基突

变导致的蛋白蛋白相互作用减弱可诱导并增强蛋白核酸相互作用，从而导致转录因子对特异序列的选择性

增强, 这一结论与实验观察和生物信息学分析结果一致；单核酸多态性可导致 DNA 大沟和小沟的宽度和深

度发生变化，从而传递和影响附近的小沟宽度，影响转录因子的结合强度，从而导致基因的上调和下调。

这些研究成果对于揭示转录因子组合调控机制，理解转录调控过程具有积极意义，同时也对相关实验研究

和药物开发具有借鉴意义。

关键字:分子动力学,转录调控,转录因子


164

AutoT&T v.2: An Efficient and Versatile Tool for Lead Structure Generation

and Optimization

王任小

中科院上海有机化学研究所

摘要

In structure-based drug design, automated de novo design methods are helpful tools for lead discovery as well as

lead optimization. In a previous study (J. Chem. Inf. Model., 2011, 51, 1474–1491), we reported a new de novo

design method, namely Automatic Tailoring and Transplanting (AutoT&T). It overcomes some intrinsic problems

in conventional fragment-based build-up methods. In this study, we describe an upgraded version, i.e. AutoT&T2.

Structural operations conducted by AutoT&T2 have been largely optimized by introducing several new algorithms.

As result, its overall efficiency in multi-round optimization jobs has been speeded up by a few thousand folds.

With this improvement, it is now practical to conduct structural crossover among multiple lead molecules by using

AutoT&T2. Three different test cases are described in this study, which demonstrate the new features and versatile

applications of AutoT&T2. The AutoT&T2 software suite is available to the public. Besides, a web portal for

running AutoT&T2 on-line is provided at http://www.sioc-ccbg.ac.cn/software/att2 for testing.

关键字:structure-based drug design,de novo design


165

水溶性寡聚苯撑乙烯在克服肿瘤细胞耐药性方面的设计与研究

周凌云


摘要

化疗耐药常发生于癌症病人治疗期间，导致许多肿瘤常规化疗效果差，预后不良等困扰临床的重要难题。

起初大部分患者化疗治疗方法有反应，肿瘤缩小或是病情稳定。然而，耐药在 6-12 月内有不同程度的发生，

出现了针对靶点治疗的常见并发症，阻碍了长期治疗的成功性，随后癌症细胞会继续发生，直至患者死亡。

已证明或观察到的耐药机理有：耐药细胞对药物靶点修饰、突变使得药物对靶点亲和性降低，增强药物代

谢，增强某一种或某一类药物代谢作用酶表达，增强药物外排等。

关键字:寡聚苯撑乙烯,肿瘤耐药


166

Research on Aggregation of Human Chemokine Receptor CCR3

李计强，ZhouShitan ,葛保胜，黄方





摘要

G protein-coupled receptors (GPCRs) comprise the largest family of integral membrane proteins. They function as

signal messengers and play crucial roles in various physiological processes. We studied CCR3 aggregation in vitro

and vivo, the study will be an important theoretical basis for the human drug design targeting CCR3. In order to

study the aggregation of human chemokine receptor CCR3, we constructed the CCR3-ECFP, CCR3-EYFP

fluorescent protein expression vector, those two recombinant vector were transfected and expressed in HEK293

cells after the optimization of transient transfection. Confocal fluorescence microscopy analysis showed that CCR3

fluorescent fusion protein uniformly distributed in the cytoplasm and cell membrane. FRET analysis showed that

the fluorescence resonance energy transfer does occur between CCR3-ECFP and CCR3-EYFP, which proved the

aggregation phenomenon of CCR3 in living cells. When the receptor donor ratio was about 0.6, the FRET ratio got

half of the maximum. Then we also examined the impact of CCR3 agonists CCL11 and CCL24, and neutral

agonists SB297006 and SB328437 on the aggregation process. The study found that both the different types of

agonists, agonists concentration and duration of stimulation cannot change the aggregation process of CCR3 in

living cells significantly, which suggested that there is no positive connection between CCR3 aggregation and

ligand binding. We also enlarge cultured the T-REx-293 cell line which stably transfected human CCR3, by using

Ni affinity chromatography and size exclusion chromatography we obtained high purity CCR3 protein. Then

Alexa Fluor 488 and Alexa Fluor 647 dyes were used to label the N-terminal of purified CCR3 respectively, then

the CCR3 aggregation was detected in surfactant solution. We also detected the aggregation of fluorescently

labeled CCR3 in surfactant solution. After FRET analysis we obtained the kinetic parameters of the aggregation

process, the K value is 3.96 × 10-4 s-1.

关键字:G protein-coupled receptors,Human chemokine receptor type 3,Aggregation


167

Effect of calcium ions on the nanostiffness of articular cartilage

庞祥超 , 唐斌

Department of Materials Science and Engineering, South University of Science and Technology of China,

Shenzhen 518055, China

Department of Materials Science and Engineering, South University of Science and Technology of China,

Shenzhen 518055, China

摘要

Calcium is one of the major elements in human body, and critical in the biological and physiological functions.

Soft tissue hardening due to calcification has been reported in various diseases. However, the quantitative

relationship between the mechanical properties of soft tissues and calcification has not yet been fully understood.

In this study, using human articular cartilage as prototype material, the relationship between the ex vivo calcium

concentration and the nanostiffness of soft tissues and collagen fibrils were investigated by indentation-type

atomic force microscopy. It is found that the nanostiffness of tissue and collagen fibrils show a significant

dependence on concentration of calcium ions, when it is higher than the normal serum calcium concentration.

Structural observation of collagen fibrils indicated that the increase of nanostiffness should be the result of the

increase of crosslinking with the introduction of calcium among collagen molecules.

关键字:calcium ions,nanostiffness,articular cartilage,collagen fibrils


168

The crystal structure of the respective permease YknZ extracellular domain

from Bacillus amyloliquefaciens

许永斌

大连民族大学

摘要

Bacillus possesses the peptide toxin Sporulation-Delaying Protein (SDP), which can kill cells within a biofilm to

support continued growth, thereby delaying the onset of biofilm sporulation. The four-component transporter

YknWXYZ acts as a major SDP efflux pump to protect cells against the endogenous SDP toxin, for which YknYZ

is a non-canonical ATP-binding cassette (ABC)-type transporter. YknYZ consists of the following two

components: (1) an individual protein (YknY) and (2) a respective permease (YknZ). To date, the crystal structure,

molecular function, and mechanism of action of the integral membrane protein YknZ remain to be elucidated. In

this study, to characterize the structural and biochemical roles of YknZ in the functional assembly of YknWXYZ,

we predicted and overexpressed the YknZ extracellular domain. We determined the crystal structure of B.

amyloliquefaciens YknZ at a resolution of 2.0 Å. The structure revealed that the YknZ extracellular region exhibits

significant structural similarity with the MacB periplasmic domain, which is a non-canonical ABC-type transporter

in the tripartite macrolide-specific efflux pump in Gram-negative bacteria. We also found that the YknZ

extracellular domain can directly bind to an extracellular component of YknX. This structural and biochemical

study provides insights into the assembly of YknWXYZ, which may be relevant to understanding cannibalistic

peptide toxin resistance in Bacillus and controlling bacterial growth.

关键字:four-component transporter YknWXYZ,ABC-type transporter


169

RGD 多肽靶向的超支化聚乙烯亚胺纳米探针的制备及其肝肿瘤

SPECT/CT 双模态诊断

周本青 , 史向阳 , 王瑞芝 , 王小林

东华大学

东华大学

复旦大学附属中山医院

复旦大学附属中山医院

摘要

功能成像（PET 或 SPECT）与结构成像（CT 或 MRI）的有机结合是目前疾病诊断的发展趋势之一，能有

效提高疾病诊断的准确度 [1, 2]。在本研究中，我们采用 RGD 多肽、聚乙二醇和 DTPA 部分修饰的超支化

聚乙烯亚胺（PEI）高分子为平台，通过在其内部包裹金纳米颗粒用于 CT 成像，在其表面修饰的 DTPA 配

体分子标记 99mTc 用于 SPECT 成像。我们通过各种手段对得到的多功能纳米颗粒进行表征，发现金核纳

米颗粒尺寸分布均匀，平均粒径为 2.6 nm（Fig. 1a），其水溶液具有良好的胶体稳定性，并且在给定浓度

范围内无明显细胞毒性（[Au] = 0-200 M）。体外细胞吞噬实验证明，RGD 多肽修饰的金纳米颗粒（RGD-Au

PENPs）能靶向识别 αvβ3 整合素高表达的细胞（HCC-LM3 细胞）。体内 CT 成像实验发现，在相同的给

药时间里，静脉注射 RGD-Au PENPs 的裸鼠的肝肿瘤部位的 CT 值比静脉注射非靶向 Au PENPs 的裸鼠的

要高（Fig. 1b）；体内 SPEC 成像实验发现肝肿瘤部位的 SPECT 信号强度随给药时间而递减，并在相同的

给药时间里，静脉注射 RGD-99mTc@Au PENPs 的裸鼠的肝肿瘤部位的 SPECT 信号强度比静脉注射

99mTc@Au PENPs 的裸鼠的要高（Fig. 1c），说明 RGD 修饰的金纳米颗粒可以有效靶向原位肝肿瘤。组

织分布和病理切片研究表明，该纳米颗粒主要通过脾、肝、肾代谢，且主要器官和组织在注射后一个月之

内未出现病理性改变，说明制备的纳米材料具有良好的器官相容性。本文所制备的基于 RGD 多肽靶向的超

支化 PEI 纳米探针具有良好的靶向原位肝肿瘤的 SPECT/CT 双模态成像效果，可潜在用于不同生物体系的

精确成像诊断。

关键字:聚乙烯亚胺,CT 成像,SPECT 成像,金纳米颗粒,RGD 多肽


170

基于环糊精的多价态结合抗血栓药物载体的设计

李莉

首都医科大学

摘要

生物体内糖配体与蛋白之间可以通过多价效应的协同作用增强它们之间的亲和性、特异性，产生所谓的“多

价效应”1。生物系统中的多价作用的强度可能比一个低分子量的配体与一个蛋白的单一作用或是他们几个

单一作用的加和都高得多。环糊精的主面(C-6)和次面(C-2，C-3)的多个羟基可以作为功能修饰的位点，因

此环糊精可以作为分子脚手架将多个功能基团通过环糊精这个建筑块偶联生成具有多价团簇结构的环糊精

衍生物 2。一类四氢异喹啉生物碱类化合物可以表现出抗血小板聚集活性。我们将七个四氢异喹啉羧酸通

过共价键偶联到 β-环糊精主面边臂上形成多价态结合的抗血栓药物载体，通过多个药效团对同病变位点的

多价态结合作用可以增加载药量并提高药物在血浆中的稳定性和药效。

关键字:环糊精,多价态,四氢异喹啉羧,抗血栓


171

Non-B DNA/卟啉类配体相互作用的瞬态光谱研究

秦廷箫 , 宋迪 , 刘坤辉 , 苏红梅





摘要

在正常的生理条件下，DNA 主要是以 Watson-Crick 碱基配对的形式，以右手双螺旋的结构存在，这类经典

的DNA结构被称为B-DNA。然而，具有重复碱基的DNA序列在一定的条件下会折叠成G-quadruplex，i-motif，

Z-DNA 等非经典的 DNA 结构，这类 DNA 被称为 Non-B DNA。Non-B DNA 的形成对生物基因的转录和复

制过程有巨大的影响。由于 Non-B DNA 可以作为抗癌药物的靶点，在癌细胞中具有抑制端粒酶的活性，控

制致癌基因表达的作用。配体分子稳定 Non-B DNA，使得这类配体分子成为潜在的抗癌药物。研究配体分

子与 Non-B DNA 的相互作用有很多探测方法。我们采用瞬态光谱的方法研究了卟啉类配体与两种 Non-B

DNA (i-motif 和 Z-DNA)的作用模式。从微观层面揭示了配体与 Non-B DNA 的相互作用机理。这对于理解

配体稳定 Non-B DNA 的微观机理具有重要意义。

关键字:Non-B DNA,卟啉配体,瞬态吸收光谱


172

The transient ion-pair species captured in the oxidation process of DNA

Guanine

节家龙 , 刘坤辉 , 苏红梅


北京师范大学化学化工学院

北京师范大学化学化工学院

摘要

Understanding the reaction mechanism of Guanine (G) in DNA with oxidant radicals is imperative when trying to

elucidate the potential oxidation damage on DNA. Previously, a pathway was theoretically suggested that includes

an ion-pair intermediate. However, up till now, such an ion-pair intermediate has not been observed

experimentally due to its expected instability. In this work, the oxidation process for G by Cl2-•/Cl• radicals was

studied at low temperatures to capture the unstable intermediate via nanosecond flash photolysis. A new strong

absorption around 570 nm at 230 K was observed. It was assigned to the ion-pair G+•…Cl- species based on

TD-DFT calculation and the analysis of the experiment. Through the spectra at low temperatures, both the addition

pathway relevant to the ion-pair intermediate and one-electron-oxidation pathway were manifested. Furthermore, a

kinetic parameter of this new species, the decay activation barrier 21.9 ± 2.7 kJ/mol was then determined. To our

knowledge, it is the first time that such an ion-pair intermediate was experimentally captured and characterized.

The direct experimental evidence can provide illuminations for the deeper understandings of DNA oxidation

damage chemistry.

关键字:ion-pair intermediate,Guanine,transient spectra, low temperature


173

A “Flip-Flop” Mechanism of a Double-Helix Foldamer’s Disassembly

赵东波，DongHao , LiShuhua

Nanjing University

Nanjing University

Nanjing University

摘要

Foldamers, defined as artificial molecular architectures inspired by the structures and functions of biopolymers,

have been a hot button in supramolecular chemistry. They fold into conformationally ordered states in solutions.

However, there are only some sporadic studies revolving around the folding equilibrium as well as the folding

pathways and kinetics. Here, taking aromatic oligoamides as illustrations, we aim to delve into the unfolding

mechanism of a double-helix foldamer by employing molecular simulations. In this work, the disassociation free

energy profile of two monomers from a dimer is determined from the potential of mean force calculations with

restraints. Our data reveal that the dynamic disassembly process is via a “flip-flop” mechanism by varying the

dihedrals, and two helix chains dissociate synchronously. The unfolding pathway is further characterized by NMR

signals calculated with the generalized energy-based fragmentation (GEBF) method, a low scaling quantum

chemistry method designed for large systems including supramolecules. The present work provides information

about dynamic assembly of aromatic oligoamides at atomic level, and is helpful to establish design principles for

well organized molecular architectures.

关键字:supramolecular chemistry,foldamer,disassembly


174

A multifunctional targeted MRI/CT dual-mode imaging probe for cancer

diagnosis and in situ real-time treatment

岳鲁丹，WANGJinlong , 郑秀文

Linyi University

Linyi University

Linyi University

摘要

Here, we have prepared a FePt/GO-based nanocomposite as a potential targeted theranostic agent for cancer

treatment. Using the FA targeting function and FePt magnetic properties, the as-prepared nanocompsites endowed

the dual functions of targeting and MRI diagnosis. And also, the presence of Pt show the possibility of the

as-prepaed nanocomposites as CT contrast agent for real-time imaging . After endocytosed intracellular, the

activated Fe have been released due to the low pH value in the cancer cells(pH=4.7), which will catalyze hydrogen

peroxide into ROS based on the Fenton reaction, which could damage intracellular lipids, thus achieving cells

lysed. It was found that the FePt/GO-based nanocomposite can inhibit tumor growth. The survival rate of MCF-7

cells drops down to 49.5%, after cultured with FePt/GO-based nanocomposite for 6 hours at the Fe concentration

of 40μg / ml, indicating that the IC50 of the FePt/GO-based nanocomposite is about 40 ug/ml. However, the

survival rate drops down to 8% when the Fe concentration reaches 100 ug / ml, indicating that the FePt/GO-based

nanocomposite showed significant toxicity to tumor cells.

关键字:MRI/CT,theranostic probe


175

探讨白细胞介素 IL-21 特殊抗体提升机体免疫力的机理

崔艳芳 , 梅龙灿 , 耿晖

华中师大

华中师大

华中师大

摘要

高等动物免疫系统不仅能对病毒细菌等病原体做出固有免疫反应，而且具有适应性免疫能力即在受到相同

病原体再次侵犯的时候能够快速做出免疫应答。自 2000 年发现以来，IL-21 已被证实对于机体的固有和适

应性免疫都非常重要。其分子具有抗癌抗病毒等功能，其受体在 DC、NK、B、T 等多种细胞上都有表达。

辅助性 TFH 细胞通过分泌细胞因子 IL-21 作用于 B 细胞，产生长效浆细胞，分泌高亲和性抗体储存在体液

和粘膜中以保持抗体水平. 所以 IL-21 是调节产生浆细胞以维持长效体液免疫抗体水平的关键细胞因子。尤

其在弱病毒慢性感染情况下， IL-21 对于维持 CD8 T 的持久杀伤活性起关键作用。所以对 IL-21 的认识将

有助于对 HPV 感染导致的肝癌及 HIV 感染导致的 AIDS 疾病的研究。与普通中和性抗体通常阻断抗原分子

的功能不同，有一类加和性抗体可以提升抗原分子的活性。前期发现的 IL-21 的加和性抗体 KJ 可提高体内

活性 10 倍，明显提升机体自身免疫能力，但是增效机理不明阻碍了对其进一步开发。我们应用 x-射线、蛋

白质工程及理论计算等手段分析了 IL-21 与增效单抗的复合物结构特点，完善了增效机制模型，帮助有效

开发该抗体的应用。Fig1 显示抗体-抗原-受体复合物的结构. Fig2 显示该增效抗体的增效结构域.

关键字:细胞因子,增效抗体,蛋白质结构


176

Binding to bovine serum albumin protects β-carotene against oxidative

degradation

常慧婷，张建平

Renmin University of China

Renmin University of China

摘要

Carotenoids are important nutrients with antioxidative properties. Serum albumin is the most abundant protein in

blood plasma and serves as a depot and transport protein for numerous endogenous and exogenous compounds.

Association of carotenoids with proteins may involve redistribution of electrons in the conjugated double bonds of

the carotenoids. Such perturbation of electrons may affect the configuration of the carotenoids and the structure of

the protein. The ease of oxidation of the carotenoids will accordingly also be affected. The effects on the oxidative

stability of β-carotene (β-Car) when associated to bovine serum albumin (BSA) were studied by combining

relevant spectroscopic methods with continued wave and time resolved photochemical techniques. Binding to BSA

was found to protect β-Car efficiently against photobleaching. Transient absorption spectroscopy confirmed less

bleaching of β-Car on the μs timescale in the presence of BSA, while kinetics of triplet-state β-Car was unaffected

by presence of oxygen. The protection of β-Car against this type of reaction seems accordingly to depend on

dissipation of excitation energy from an excited state into the protein matrix. Quenching of tryptophan (Trp)

fluorescence by β-Car suggests involvement of Trp in binding of β-Car to BSA through hydrophobic interaction,

and it may be the β-Car aggregates rather than monomer which quench the fluorescence by static process. Bound

β-Car increased the random coil fraction of BSA at the expense of α-helix, affecting the β-Car configuration.

关键字:β-carotene, protein binding,photodegradation,bovine serum albumin


177

OmpC is expansive with the help of chaperone SurA

李耕


摘要

The β-barrel outer membrane proteins (OMPs) are located on the outer membrane of Gram-negative bacteria with

biological significance. SurA protein has been identified as a periplasmic chaperone that participates in the

translocation of OMPs from E. Coli’s inner membrane to outer membrane[1]. Using single molecule fluorescence

resonance energy transfer (smFRET), we studied the interaction between outer membrane protein C (OmpC) and

SurA with/without the presence of urea. We found that just like in urea denaturing condition, OmpC that binds to

SurA showed an expansive conformation. This phenomenon may be important in understanding the mechanism of

the biogenesis of OMPs.

关键字:OmpC,SurA,smFRET,expansive conformation


178

Scanning single-molecule fluorescence correlation spectroscopy enables

kinetics study from microseconds to seconds

毕慧敏


摘要

Single-molecule fluorescence measurements have been widely used to explore kinetics and dynamics of biological

systems. Among them, single-molecule imaging (SMI) is good at tracking processes slower than tens of

milliseconds, whereas fluorescence correlation spectroscopy (FCS) is good at probing processes faster than

submilliseconds. However, there is still shortage of simple yet effective single-molecule fluorescence method to

cover the time-scale between submilliseconds and tens of milliseconds. To effectively bridge this millisecond gap,

we developed a single-molecule fluorescence correlation spectroscopy (smFCS) method that works on

surface-immobilized single molecules through surface scanning. We validated it by monitoring the classical DNA

hairpin folding process. With a wide time window from microseconds to seconds, the experimental data are well

fitted to the two-state folding model. All relevant molecular parameters, including the relative fluorescence

brightness, equilibrium constant, and reaction rate constants, were uniquely determined.

关键字:FCS,single molecule detection,hairpin folding


179

Molecular Dynamic Simulations of the Trp-cage Folding/unfolding

Mechanism and its Folding-related Problems Based on PDB Coil Library

吴晓敏，张海军

Huaibei Normal University

Huaibei Normal University

摘要

The major driving force of protein folding depends on their inter-residue interactions, especially for

sidechain-sidechain interactions. Although the Trp-cage is a fast-folding mini-protein containing merely 20 amino

acid residues, it exhibits an extremely complex interaction network between residues with different types of

side-chain orientation. Because current force fields exhibit accuracy inadequacies in the descriptions of atomic

interactions, it still remains a matter of debate at what stage of folding the helix, hydrophobic cluster and

salt-bridge is being conclusively formed in its possible folding mechanisms. Herein, independent MD simulations

with these two OPLSAA/L and OPLSAA/C force fields were conducted to investigate their on-pathway and

off-pathway folding/unfolding events and compared them with respect to their folding accuracy and efficiency.

The results indicates that the Trp-cage mini-protein can fold towards into its native on its fast-folding pathway

under OPLSAA/C force field, whereas could not correctly fold within 500 ns but unfold into a overwhelmingly

populated non-native state under OPLSAA/L force field. Nonetheless, their different transition paths on the

free-energy profiles support a two-state model of this mini-protein. As confirmed by interaction analysis, the

hydrophobic and hydrogen bonding interactions as well as long-range native contracts contribute a lot to Trp-cage

fast-folding transition under the OPLSAA/C force field.

关键字:Protein folding,Molecular Dynamics,Interaction network,Long-range native contacts


180

PEI–folic acid modi fied carbon nanodots for cancer cell-targeted delivery

and two-photon excitation imaging

王晶

上海光机所

摘要

Polyethyleneimine conjugated folic acid (PEI –FA) was coated onto the surfaces of fluorescent carbon nanodots

(CDots) under neutral conditions through electrostatic interactions between the partially charged amino groups of

PEI –FA and the carboxyl ( –COOH) groups of the CDot surfaces. Because of the high abundance of folate

receptors (FR) in cancer cells, folic acid (FA) was used as the targeting ligand to enhance the CDots' binding

capability and penetration into the target cancer cells. We evaluated the amount of particles internalized by cancer

cell lines displaying various levels of folate receptors. Two-photon excitation microscopy images revealed that the

uptake of CDot–PEI–FA by FR-positive KB cancer cells was much higher than that by FR-negative A549 cancer

cells. Moreover, quantitative flow cytometry analysis confirmed the receptor-mediated targeted delivery of the

nanoparticles into diff erent FR-expressing cells. The internalization of particles was ten-fold higher in the

FR-positive KB cancer cells compared to that in the FR-negative A549 cancer cells; the di fference was significant

enough to be of biological importance. These preliminary results demonstrate the promising potential of CDot

–PEI–FA for FR-positive cancer cell line diagnosis.

关键字:carbon nanodot,targeting delivery,imaging


181

Understanding GPCR diversity and ligand specificity from the big data in

virtual screening

周庆同 , 赵素文

上海科技大学 iHuman 研究所

上海科技大学 iHuman 研究所

摘要

As the most important transmembrane signaling modulator, G protein-coupled receptors (GPCRs) are the most

valuable therapeutic targets while GPCR-targeting drugs account for more than 30% of prescription

pharmaceuticals on the market. Huge efforts on GPCR biochemical functions research and crystallography,

high-throughput screening, pharmaceutical chemistry led to better understanding of GPCR signaling complexity

and ligand specificity. To understand the structural diversity and ligand specificity among GPCRs, we performed

structure-based virtual screening for twenty-one kinds of GPCR. By analyzing the big data of virtual screening

results, we observed each GPCR has its unique ligand preference in MW, TPSA and other molecular descriptions,

which derived from the particular structure of the ligand-binding pocket. By comparing the virtual screening

results, we found the active states of GPCR generally tended to have special features for ligands binding. Based on

these results, we designed a computational strategy GPCRLe (GPCR ligand examiner) to predict the potential

GPCR targets for certain compound, which could be used in GPCR-related drug discovery.

关键字:GPCR,virtual screening,drug discovery


182

smFRET study of interaction between M.HhaI and dsDNA

何姗珊

北京大学

摘要

DNA methylation has attracted much attention due to its important role in epigenetic processes. M.HhaI is one of

the DNA methyltransferases in bacteria, which catalyzes the methylation of C5 of the inner cytosine in GCGC

sequence. Lots of equilibrium and kinetic studies on M.HhaI have been carried out by using ensemble techniques.

However, important details could be missed in ensemble studies. We plan to study the interaction between dsDNA

and M.HhaI by using single molecule fluorescence resonance energy transfer (smFRET). As the crystal structure

shows[1], upon binding the substrate dsDNA, significant conformational change happens in M.HhaI—the closure

of the catalytic loop. As the first step, by double labeling a Cy3-Cy5 FRET pair and conducting smFRET studies,

we observed this conformational change at single molecule level, which paves a road for further dynamic studies

at single molecule level.

关键字:smFRET,M.HhaI


183

Detection of bound chaperones by single-molecule FCS

潘思辰 , 赵新生

Peking university

Peking university

摘要

In gram-negative bacteria, outer membrane proteins (OMPs) have various critical functions, so study about their

quality control in biogenesis is of great importance. There are three kinds of molecular chaperones to protect

OMPs in periplasmic. Previously published model[1] revealed that SurA can transfer OMPs to outer membrane

directly. More interestingly, SurA and Skp can transfer OMPs to DegP. DegP degrades mis-folded OMPs and

protect pre-folded OMPs to outer membrane, but many details in the mechanism are still poorly understood.

Traditional ensemble methods are difficult to study the process because of mixture of many subpopulations.

Driven by the problem, we develop a subpopulation-specific single-molecule method which can resolve molecules

with different conformations using single-molecule fluorescence resonance energy transfer (smFRET) and then

fluorescence correlation spectroscopy (FCS) of specific FRET region can be calculated to get molecular weight

and bound states.

关键字:OMPs,chaperones,FRET,FCS,subpopulation


184

Thermochromatium tepidum 外周捕光天线蛋白 LH2 在脂质体及表面活

性剂胶束中的光谱性质对比

王鹏 , 霍一林 , 张建平

中国人民大学化学系



摘要

嗜热紫色光合细菌 Thermochromatium (Tch.) tepidum 的外周捕光天线 LH2 是含有类胡萝卜素和细菌叶绿素

的色素-蛋白复合物，在近红外区有很强的细菌叶绿素吸收谱带 B850-Qy；该谱带对温度、离子等环境因素

十分敏感，因而可用作检测蛋白与环境相互作用的光谱探针。我们通过动态光散射、透射电子显微镜、吸

收光谱和拉曼光谱等手段对比研究了处于表面活性剂胶束中和脂质体双分子层脂膜中的 Tch. tepidum LH2

的光谱响应：与表面活性剂胶束相比，双分子层脂膜中 LH2 的 spirilloxanthin（一种含有 13 个共轭双键的

类胡萝卜素）构象有明显差异；表面活性剂以及磷脂分子端基的荷电状态对 B850-Qy 吸收谱有显著影响；

Ca2+结合导致 B850-Qy 吸收谱带红移和增色，而 H+结合影响该吸收谱带的趋势则相反。对 LH2 脱辅基蛋

白氨基酸序列分析表明，Ca2+和 H+的结合位点可能位于 α 脱辅基蛋白的 C-端一侧。B850-Qy 吸收谱带对

Ca2+和 H+的响应特性可能与 Tch. tepidum 适应其生存环境的能力有关。

关键字:Thermochromatium tepidum,外周捕光天线 LH2,表面活性剂,脂质体


185

β-胡萝卜素聚集体制备及其光物理性质研究

张迪 , 王鹏

中国人民大学化学系，北京市中关村大街 59 号

中国人民大学化学系，北京市中关村大街 59 号

摘要

类胡萝卜素是自然界广泛存在的重要光合色素之一，在光合作用中起到辅助捕光、传能以及光保护的作用。

类胡萝卜素在天然光合体系中常常以聚集体形式存在，而聚集态的类胡萝卜素经常具有从一个单重激发态

裂分成两个三重态的现象，即单线态裂分。这一现象可能会大幅度提高相应的光量子产率，从而可被应用

于光电转换功能体系中[1]。本研究采用阳离子表面活性剂 CTMAB 首先在水中形成胶束、进而用丙酮溶解

胡萝卜素导入胶束、再透析除去丙酮的方法，获得被表面活性剂胶束包裹、稳定存在的胡萝卜素聚集体的

悬浮溶液。紫外可见吸收光谱研究表明 β-胡萝卜素主要形成 J-型聚集体，相比于单体溶液，在510 nm 处

产生新的吸收峰。激光共振拉曼研究表明，选择性激发 510 nm，与单体相比，聚集体中类胡萝卜素端基附

近的相关振动模式强度发生变化，由此可以推测聚集体的结构形式。选择性激发 510 nm，纳秒时间分辨光

谱可以直接得到类胡萝卜素聚集体三线态吸收的光谱特征，其最大值出现在约 550 nm，比相应-胡萝卜素

单体的三线态吸收红移 40 nm；聚集体三线态寿命约为 1.1 μs（除氧），远短于单体的三重态寿命（除氧条

件下为 10μ s）；聚集体三线态寿命对氧气不敏感。类胡萝卜素三重态产生的超快动力学机制需要进一步采

用飞秒瞬态吸收光谱进行研究。

关键字:单线态裂分,β-胡萝卜素聚集体,激光共振拉曼,纳秒时间分辨吸收光谱,三线态吸收


186

Dispersed OmpT may be partially folded

卜佩璇，赵新生

College of Chemistry and Molecular Engineering and Biodynamic Optical Imaging Center (BIOPIC), Peking

University, Beijing 100871

College of Chemistry and Molecular Engineering and Biodynamic Optical Imaging Center (BIOPIC), Peking

University, Beijing 100871

摘要

It is believed that outer membrane proteins in Gram-negative bacteria are protected by chaporones during their

translocation through the periplasm because they are structureless and prone to aggregation. The previous work on

OmpC supported such an opinion. However, recently we found that OmpT has less tendency to aggregate and may

be partially folded in its dispersed form. By using single molecule fluorescence resonance energy transfer

(smFRET), the equilibrium denaturation of OmpT induced by urea has been investigated. Double-cysteine

mutant(S1C/F297C) of OmpT is engineered and labeled with FRET dyes. We observed subpopulations of

denatured and partially folded form of OmpT and the two subpopulations show two-state transition as urea

concentration changes. These resluts may help better understanding of outer membrane protein folding.

关键字:OmpT,smFRET,urea denaturation,partial folding


187

Tertiary Structure Formation in SRV-1 RNA Pseudoknot Increases

Mechanical Stability and −1 Ribosomal Frameshifting Efficiency

钟振声，杨丽霞，陈刚




摘要

Many RNA viruses including Simian Retrovirus type 1 (SRV-1) utilize minus-one ribosomal frameshifting as an

alternative translation mechanism to generate stable ratios of structural and catalytic proteins. The detailed

mechanism of minus-one ribosomal frameshifting is still not well understood. The SRV-1 frameshifting

pseudoknot is located in the overlapping region of gag and pol genes and plays critical roles in stimulating

frameshifting. We applied single-molecule force spectroscopy and steered molecular dynamics simulation to probe

the mechanical stability of the wildtype SRV-1 frameshifting RNA pseudoknot and its mutants. In addition, we

carried out ensemble thermal denaturation and native polyacrylamide gel electrophoresis studies. Our studies

reveal that the minor-groove base triple formation in the pseudoknot enhances the structural compactness and

mechanical stability. The −1 frameshifting efficiency is positively correlated with one-step unfolding rupture force

and inversely correlated with the unfolding rate, consistent with the fact that ribosome is a force-generating

molecular motor with helicase activity.

关键字:RNA pseudoknot,ribosomal frameshifting,optical tweezers


188

附：参会人员名录（会前注册版）

安海龙河北工业大学生物物理研究所 [email protected]

安琪中国地质大学（北京） [email protected]

白昊天中国科学院化学研究所 [email protected]

毕慧敏北京大学化学与分子工程学院 [email protected]

别丽华华中农业大学信息学院 [email protected]

卜佩璇北京大学 [email protected]

蔡明军中国科学长春应用化学研究所 [email protected]

曹美文中国石油大学（华东） [email protected]

柴燃河北工业大学 [email protected]

常慧婷中国人民大学 [email protected]

陈春来清华大学 [email protected]

陈刚 Nanyang Technological University [email protected]

陈缙泉华东师范大学 [email protected]

陈静中国科学院上海药物研究所 [email protected]

陈莉莉上海药物研究所 [email protected]

陈慕浙江工业大学 [email protected]

陈小小佛山市南海环境工程有限公司 [email protected]

陈艳艳中国科学院化学研究所 [email protected]

陈长军华中科技大学 [email protected]

成永强河北大学化学学院 [email protected]

程靓中国科学院化学研究所 [email protected]

迟海霞中国石油大学（华东） [email protected]

崔雪静中国石油大学（华东）生物工程中心 [email protected]


189

崔艳芳华中师大 [email protected]

单玉萍长春工业大学 [email protected]

杜利凯华中农业大学 [email protected]

杜凌云河北大学 [email protected]

段新瑞陕西师范大学 [email protected]

樊晓阳武汉大学化学院刘义教授课题组 [email protected]

范一冰河北工业大学理学院生物物理研究所 [email protected]

冯世亮中国科学院力学研究所 [email protected]

盖锋 University of Pennsylvania [email protected]

盖文卓 Tianjin osenbo tech. LTD. [email protected]

高军华中农业大学 [email protected]

高涛武汉大学 [email protected]

高天武汉大学 [email protected]

高婷娟华中师范大学 [email protected]

高毅勤北京大学 [email protected]

耿浩河北大学 [email protected]

龚为民中国科学技术大学 [email protected]

龚洲中国科学院武汉物理与数学研究所 [email protected]

韩莉中科院上海有机化学研究所 [email protected]

韩晓军哈尔滨工业大学 [email protected]

郝先 Institut Pasteur, Paris, France [email protected]

郝长春陕西师范大学生物物理实验室 [email protected]

何程智天津大学 [email protected]

何欢武汉大学化学与分子科学学院 [email protected]

何姗珊北京大学化学学院 [email protected]


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贺萍中国科学院化学研究所 [email protected]

贺强哈尔滨工业大学 [email protected]

侯旭厦门大学 [email protected]

胡霞中国科学技术大学化学物理系 [email protected]

胡中进江汉大学 [email protected]

黄方中国石油大学（华东） [email protected]

黄建国浙江大学化学系 [email protected]

黄蓉武汉大学 [email protected]

黄旭辉香港科技大学深圳研究院 [email protected]

黄艳武汉大学 [email protected]

姬燕云中国石油大学华东 [email protected]

蒋帆北京大学深圳研究生院 [email protected]

蒋风雷武汉大学化学与分子科学学院 [email protected]

蒋耀文东南大学 [email protected]

节家龙中国科学院化学研究所 [email protected]

解晓雯北京大学 [email protected]

金建成武汉大学 [email protected]

康玉浙江大学 [email protected]

来鲁华北京大学化学与分子工程学院 [email protected]

兰兰中国科学院生物物理研究所 [email protected]

李栋中国科学院，生物物理研究所 [email protected]

李耕北京大学化学与分子工程学院 [email protected]

李皓然中国石油大学（华东） [email protected]

李烆一北京大学 [email protected]

李晖北京理工大学 [email protected]


191

李计强中国石油大学（华东） [email protected]

李剑峰中国科学院大学 [email protected]

李菁菁同济大学 [email protected]

李莉首都医科大学 [email protected]

李平山东师范大学 [email protected]

李强国湘南学院 [email protected]

李盛亮中国科学院化学研究所 [email protected]

李世新中国石油大学（华东） [email protected]

李享华中师范大学化学学院 [email protected]

李贞武汉大学 [email protected]

林冬冬复旦大学 [email protected]

吝晓君中国石油大学(华东) [email protected]

刘东升 iHuman institute, ShanghaiTech University [email protected]

刘冬生清华大学化学系 [email protected]

刘海燕中国科学技术大学 [email protected]

刘恺河北大学 [email protected]

刘坤辉北京师范大学化学学院 [email protected]

刘礼兵 ICCAS [email protected]

刘晓红生物物理研究所 [email protected]

刘艳上海科技大学 [email protected]

刘扬中中国科学技术大学 [email protected]

刘义武汉大学 [email protected]

刘玉娇武汉大学 [email protected]

刘长林华中师范大学化学学院 [email protected]

刘志洪武汉大学 [email protected]


192

刘主浙江大学 [email protected]

柳华杰中国科学院上海应用物理研究所 [email protected]

龙勉中科院力学研究所 [email protected]

卢欢中国科学院化学研究所 [email protected]

陆瑶中国科学院大连化学物理研究所 [email protected]

陆洲中国科学院化学研究所 [email protected]

罗毅中国科学技术大学 [email protected]

马广辉上海药物研究所 [email protected]

马晓旻北京大学 [email protected]

梅晔 East China Normal University [email protected]

名洁山西大学分子科学研究所 [email protected]

牛瑞民河北工业大学生物物理所 [email protected]

牛瑞民河北工业大学理学院生物物理研究所 [email protected]

潘白龙北京大学 [email protected]

潘思辰北京大学 [email protected]

庞祥超南方科技大学 [email protected]

彭俊辉中国科学技术大学生命科学学院 [email protected]

齐伟曲阜师范大学 [email protected]

齐志北京大学 [email protected]

琪其格中国科学院化学研究所 [email protected]

秦廷箫中国科学院化学研究所 [email protected]

曲晓刚中科院长春应用化学研究所 [email protected]

权春善大连民族大学 [email protected]

权春善大连民族大学 [email protected]

任浩中国石油大学（华东） [email protected]


193

阮浩北京大学 [email protected]

邵昉伟 Nanyang Technological University [email protected]

邵婧鑫哈尔滨工业大学、国家纳米科学中心 [email protected]

邵婧鑫哈尔滨工业大学/国家纳米科学中心 [email protected]

石发展中国科学技术大学 [email protected]

石景中国科学技术大学 [email protected]

史向阳东华大学 [email protected]

史晓凡中科院上海药物研究所 [email protected]

宋迪中国科学院化学研究所 [email protected]

宋彦卓中国石油大学 [email protected]

宋珍太原师范学院 [email protected]

苏红梅北师大化学学院 [email protected]

苏敏仪中国科学院上海有机化学研究所 [email protected]

孙含中国科学院化学研究所 [email protected]

孙红哲香港大学/中山大学 [email protected]

孙润广陕西师范大学生物物理实验室 [email protected]

孙婷婷中国石油大学（华东） [email protected]

孙亚伟中国石油大学（华东） [email protected]

孙育杰北京大学 [email protected]

谈军军中国科学技术大学 [email protected]

谭砚文复旦大学 [email protected]

汤薇陕西师范大学 [email protected]

唐淳中科院武汉物理与数学研究所 [email protected]

田发林温州生物材料与工程研究所 [email protected]

田敬肖河北大学 [email protected]


194

田长麟中国科学技术大学 [email protected]

童正青华东师范大学 [email protected]

汪文婷中国科学技术大学 3 系 [email protected]

王芳芳武汉大学化学与分子科学学院 [email protected]

王宏达中国科学院长春应用化学研究所 [email protected]

王宏飞山西大学分子科学研究所 [email protected]

王建平中国科学院化学研究所 [email protected]

王建武中国科学院化学研究所 [email protected]

王江云中国科学院生物物理研究所 [email protected]

王晶上海光机所 [email protected]

王鹏中国人民大学化学系 [email protected]

王鹏飞中国科学技术大学 [email protected]

王任小中科院上海有机化学研究所 [email protected]

王任小中国科学院上海有机化学研究所 [email protected]

王申林北京大学 [email protected]

王文明山西大学 [email protected]

王文宁复旦大学 [email protected]

王晞武汉大学 [email protected]

王晓辉中国科学院长春应用化学研究所化学生

物学实验室

[email protected]

王晓瑜中国科学院化学研究所 [email protected]

王雅楠中国石油大学（华东） [email protected]

王耀坤中国科学院化学研究所 [email protected]

王云侠中国科学院化学研究所 [email protected]

位灯国华中农业大学理学院 [email protected]


195

魏东山中国科学院重庆绿色智能技术研究院 [email protected]

魏东山中国科学院重庆绿色智能技术研究院 [email protected]

魏锋江汉大学 [email protected]

翁经纬复旦大学 [email protected]

翁羽翔中科院物理研究所 [email protected]

吴富根东南大学 [email protected]

吴帅宾湖北师范大学 [email protected]

吴思中国科学院生物物理研究所 [email protected]

吴晓华中科院化学所 [email protected]

吴晓敏淮北师范大学 [email protected]

夏飞华东师范大学 [email protected]

夏文秀江汉大学 [email protected]

向迅武汉大学 [email protected]

肖长清湖北第二师范学院 [email protected]

肖长生湖北第二师范学院 [email protected]

晓刚中国科学院长春应用化学研究所 [email protected]

谢长林中国科技大学 [email protected]

邢成芬河北工业大学 [email protected]

徐海中国石油大学（华东） [email protected]

徐娟武汉大学化学与分子科学学院 [email protected]

徐玲中国科学技术大学 [email protected]

徐平勇中科院北京生物物理研究所 [email protected]

徐四川云南大学 [email protected]

徐天丹上海科技大学 [email protected]

徐燕中国石油大学（华东） [email protected]


196

徐玉林华中师范大学化学学院 [email protected]

许菲江南大学 [email protected]

许永斌大连民族大学 [email protected]

玄明君中国科学院化学研究所 [email protected]

玄明君中国科学院化学研究所 [email protected]

闫学海中国科学院过程工程研究所 [email protected]

严洁 National University of Singapore [email protected]

严以京中国科学技术大学化学与材料科学学院 [email protected]

严以京中国科学技术大学 [email protected]

杨彬中国石油大学（华东） [email protected]

杨朝勇厦门大学 [email protected]

杨春帆北京师范大学 [email protected]

杨江涛河北大学 [email protected]

杨洁中国科学院生物物理研究所 [email protected]

杨俊中国科学院武汉物理与数学研究所 [email protected]

杨丽敏中国石油大学（华东） [email protected]

杨利霞 Nanyang Technological University [email protected]

杨琪琦武汉大学 [email protected]

姚礼山中科院青岛生物能源与过程研究所 [email protected]

姚立中国科学院化学研究所 [email protected]

姚天明同济大学化学系 [email protected]

叶树集中国科学技术大学 [email protected]

叶晓东中国科学技术大学 [email protected]

尹苗苗武汉大学化学与分子科学学院 [email protected]

尹盼盼同济大学 [email protected]


197

游慧娟 National University of Singapore [email protected]

郁婷中国科学技术大学 [email protected]

袁军华中国科学技术大学 [email protected]

岳鲁丹临沂大学化学化工学院 [email protected]

岳同涛中国石油大学（华东） [email protected]

张柏雄合肥微尺度物质科学国家实验室 [email protected]

张川上海交通大学 [email protected]

张迪中国人民大学理学院化学系 [email protected]

张锋中国科学技术大学 [email protected]

张海元中国科学院长春应用化学研究所 [email protected]

张浩淼湖北武汉华中科技大学 [email protected]

张会亭中国石油大学（华东） [email protected]

张丽影大连民族大学 [email protected]

张璐香港科技大学 [email protected]

张乃霞中国科学院上海药物研究所 [email protected]

张盼盼上海艮泰信息技术有限公司 [email protected]

张鹏博中国科学院化学研究所 [email protected]

张群中国科学技术大学化学物理系 [email protected]

张婷陕西师范大学 [email protected]

张文凯北京师范大学 [email protected]

张文科吉林大学 [email protected]

张宇天津奥辛博科技有限责任公司 [email protected]

张志勇中国科学技术大学 [email protected]

章毅中国科学与技术大学 [email protected]

赵东波南京大学化学化工学院 [email protected]


198

赵红梅中国科学院化学研究所 [email protected]

赵红梅中国科学院化学研究所 [email protected] 中国科学院化

学研究所

赵丽娜中国科学院高能物理研究所 [email protected]

赵南蓉四川大学 [email protected]

赵新生北京大学 [email protected]

赵永芳中国科学院生物物理研究所 [email protected]

赵永祥中科院武汉物理与数学研究所 [email protected]

郑秀文临沂大学 [email protected]

钟桂生上海科技大学 iHuman 研究所 [email protected]

仲冬平 Ohio State University [email protected]

周本青东华大学 [email protected]

周华斌北京大学 [email protected]

周俊南京大学化学化工学院 [email protected]

周莉中国科学技术大学 [email protected]

周凌云中国科学院化学研究所 [email protected]

周庆同上海科技大学 iHuman 研究所 [email protected]

周鑫中科院化学研究所 [email protected]

朱通华东师范大学 [email protected]

庄巍中科院福建物质结构研究所 [email protected]

邹鹏北京大学化学学院 [email protected]

中国化学会 生物物理化学专业委员会 第四届全国生物物理化学会议 ·...

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中国化学会生物物理化学专业委员会第四届全国生物物理化学会议 ·...