pymine – a pymol plugin to integrate and visualize chemical and biological data for drug discovery...
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PyMine – A PyMol Plugin to PyMine – A PyMol Plugin to Integrate and Visualize Chemical Integrate and Visualize Chemical and Biological Data for Drug and Biological Data for Drug DiscoveryDiscovery
Zhijun Li, Ph.D.
Departments of Chemistry & BiochemistryUniversity of the Sciences in Philadelphia
USA
Drug discovery is a costly processDrug discovery is a costly process
http://www.chemistry-blog.com/2012/01/04/tedtalk-medicine-for-the-99-hes-about-99-wrong/.
Cheminformatics and Cheminformatics and bioinformatics can facilitate drug bioinformatics can facilitate drug discoverydiscovery
Target identification
Target modeling
In silico screening and design
Krasky et al., Genomics, 2007, 89: 36-43.
Current Approaches for Current Approaches for Bioinformatics Data IntegrationBioinformatics Data Integration
Service-oriented web approach
Data warehousing approach
Other approaches
Interface and OutputInterface and Output
Chaudhari and Li., BMC Research Notes, 2015, submitted.
Panel Interface PyMol 3D visualization Output Directory
Human Malic Acid EnzymesHuman Malic Acid Enzymes
Major enzymes in the production of NADPH
Also closely associated with the TCA cycle, a central metabolic hub
In mammalian cells, two major malic enzyme isoforms (ME1 and ME2) have been identified
Malic enzymes reciprocally Malic enzymes reciprocally module p53module p53
Jiang et al., Nature, 2013, 493: 689-695.
PyMine Study and CADD PyMine Study and CADD ApproachApproach
ME1 structure
Catalytic site
Known inhibitors
Ligand-based approach using ShapeSignature
Structure-based approach using Glide
Assay testing
SummarySummary
Developed an innovative and automated tool to integrate and visualize chemical and biological data for drug discovery.
PyMine integrates data from six high-quality chemical and biological databases and maps imported structural information onto receptor 3D structure.
PyMine imports and/or generates files that can be used directly for drug discovery projects.
https://github.com/rrchaudhari/PyMine
Future DevelopmentFuture Development
To include support for additional chemical/biological databases.
To apply inductive logic programming in order to generate and prioritize data driven hypotheses.
To automate cheminformatics workflows based on imported structural data to test generated hypothesis.
AcknowledgementAcknowledgement
PhRMA Foundation NSF NIHUPenn- ITMAT
Dr. Jun Gao
Dr. Vagmita Pabuwal
Dr. Jhenny Galan
Dr. Andrew Heim
Usha K. Muppirala
Rajan Chaudhari
Daoyuan Dong
Tejashree Redij
David Cho
Univ. of PennsylviniaDr. Wenchao Song; Dr.
Xiaolu YangCHOP
Dr. Hakon Hakonarson, Duke University
Dr. Chin-Ho Chen; Dr. Li HuangWistar Institute
Dr. Jose Conejo-GarciaUniversity of Sydney, Australia
Dr. John ChristodoulouMeharry Medical College
Dr. Hua XieUniv. of Missouri
Dr. Gerald L. HazelbauerUsciences
Dr. Zhiyu Li; Dr. Preston Moore