multiscale structural visualization with ucsf chimera · visualization-based data analysis methods...
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3/18/2005
Multiscale Structural Visualization with
UCSF Chimera
Depts. of Pharmaceutical Chemistry and Biopharmaceutical SciencesResource for Biocomputing, Visualization, and Informatics
University of California at San Francisco
Tom Ferrin
UCSF
3/18/2005
Outline
Today:
Chimera overview
Introductory demo
Bluetongue virus demo
Tomorrow - Tom Goddard “hands-on” exercise:
Chimera Volume Viewer extension
Copy of this presentation available at:
www.cgl.ucsf.edu/home/tef/talks/EMANworkshop.pdf
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Cell
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Determining the Structures of Proteins and Assemblies
Structural information from…source: measurement and modelsresolution: low or high resolution
Sali, Earnest, Glaeser, Baumeister. From words to literature in structural proteomics. Nature 422, 216-225, 2003.
Resource for Biocomputing,
Visualization, and Informatics
We are an NIH Biomedical Technology ResourceCenter, funded by the National Center for ResearchResources. We create innovative computational andvisualization-based data analysis methods andalgorithms, turn these into easy-to-use softwaretools which we distribute to the scientific community,and apply these tools for solving a wide range ofgenomic and molecular recognition problems within thecomplex sequence structure function triad.
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Sample application areas
Insight into molecular structure and function:
Protein engineering
Drug design
Biomaterials design
Annotation of protein function from sequence andstructure
Gene annotation, characterization, and interpretation:
Pharmacogenetics - understanding and prediction ofvariation in drug response due to genetic factors
Mouse gene knock-outs for modeling of human disease
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UCSF Chimera -
an Extensible Molecular Modeling System
Chimera is an extensible interactive 3-D modeling system designedto allow developers to quickly incorporate novel visualizationalgorithms and analysis tools
Chimera runs on laptops/desktops and takes maximum advantageof low-cost, state-of-the-art graphics chips
$500 today buys you 3-D interactive graphics capabilities that cost $20,000 five years ago
Chimera has extensive documentation for users and developers toenable effective scientific studies to be accomplished rapidly andwith a “low entry barrier”
UCSFChimera
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Documentation and Distribution
DocumentationExtensive User’s GuideBasic Programmer’s Guide
TrainingOn-line “Getting Started” tutorialPeriodic workshops
PlatformsWindows 98/2000/XPMac OS XLinux, SGI, HP Alpha
AvailabilityDownload from our Research Resource Center web site aftersimple “click to accept” license agreement
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Chimera’s Built-in Features
Molecular Graphics:interactively manipulate stick, ball-and-stick, CPK, ribbon representations, andmolecular surfaceshighly intuitive model translation,scaling, and rotationinteractive color editingability to save high resolution images forpresentation and publicationstereo viewing
Chemical Knowledge:determination of atom types in arbitrarymoleculesability to add hydrogen atomshigh-quality hydrogen bond identificationselection of atoms/bonds by element,atom type, functional group, and aminoacid categoryinteractive bond rotation, distance, andangle measurements
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Chimera’s Programmability/Extensibility
Chimera is designed to allow developers toquickly incorporate novel algorithms andanalysis tools
Extensions can control standard Chimerauser interface features (e.g. camera, help,menus, toolbar), as well as create their owncustom graphical user interfaces
Extensions are written in the Pythonprogramming language
– Python is easy to learn, even for noviceprogrammers
– Python is object-oriented and providesfeatures needed for development ofcomplex codes
– ~30 extensions written to date
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Learn more about Python
Python Web site:
www.python.org
Good book:
“Learning Python”
by Mark Lutz & David Ascher
Available from
www.oreilly.com/catalog/lpython2
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Sample Chimera Extension
Multalign ViewerSimultaneously displays multiple protein sequencealignments and corresponding structure superpositions,calculates and displays consensus sequence andconservation histogram, and highlights correspondingregions in both sequenceand structure space
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Sample Chimera Extension
Molecular Dynamics TrajectoriesAll built-in Chimera analysis and display capabilities alsowork with trajectories. Support is provided for a numberof common programs: AMBER, CHARMM, GROMOS,MMTK, NAMD, PDB, and X-PLOR.
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Sample Chimera Extension
Movie RecorderCapture image frames from
Chimera and assemblethese into a movie file
Formats supported:MPEG-1
MPEG-2
MPEG-4
Quicktime
(New feature in release 2104)
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Sample Chimera Extension
ViewDockRapid screening of promising drug candidates found withthe UCSF DOCK program
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Sample Chimera Extension
Volume ViewerAn extension for visualizing three-dimensional numericaldata sets
Electrostatic potential
(surfaces)
Electron density
(mesh)
Electrostatic potential
(solids)
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Sample Chimera Extension
Multiscale Modelinguseful for exploring modelsof large molecular complexescombines volumevisualization and atomicresolution capabilitiesexample systems includeviruses and chromosomesGroEL model: 14 copies ofthe monomeric GroELcrystal structure docked toa 10.3 Å electron microscopemap
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Chimera Demonstration #1
Introduction to molecular representation and basic use
Files used: 2gbp.pdb
Features illustrated:
Opening files
Selecting and displaying atoms, bonds, and surfaces
Manipulating models: rotate, translate, scale, clip
Display styles: wireframe, sticks, balls&sticks, CPK
Command line
Additional information: UCSF Chimera - A Visualization System for ExploratoryResearch and Analysis, J. Comp. Chem., 25(13):1605-1612, 2004.
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Chimera Demonstration #2
Bluetongue Virus CorePDB structure 2btv by DavidStuart’s lab (Nature 395: 470-478, 1998)
Full particle 700 Å diameter,3.5 Å resolution, 1000 crystalsand 3x106 atoms (no hydrogens)Multiscale extension makes 60copies of unit cell–Outer layer: 260 trimers of VP7 proteinin 5 symmetry classes–Inner layer: 60 dimers of VP3
Extension focuses onhierarchical structurerelationships and their selectionand display
Additional information: Software Extensions to UCSF Chimera for InteractiveVisualization of Large Molecular Assemblies, Structure, 13(3):473-482, 2005.
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Acknowledgements
Staff:Dr. Conrad Huang, Tom Goddard, Greg
Couch, Eric Pettersen, DanGreenblatt, Al Conde, Dr. ElaineMeng
Collaborators (partial list):Patricia Babbitt, UCSFWah Chiu and Steven Ludtke, BaylorJohn Sedat and David Agard, UCSFDavid Konerding and Steven Brenner,
UCB
Funding: NIH National Center for Research
Resources, grant P41-RR01081
Further information:www.cgl.ucsf.edu/chimera