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.

Data integration remains a Data integration remains a challengechallenge

www.ncbi.nlm.nih.gov

Current Approaches for Current Approaches for Bioinformatics Data IntegrationBioinformatics Data Integration

Service-oriented web approach

Data warehousing approach

Other approaches

PyMine DevelopmentPyMine Development

PyMolPyMol

Molecular visualization system

Open source

Leading software package

http://ww.pymol.org

DatabasesDatabases

UniProt

PDB

ChEMBL

IBIS

HUMSAVAR

KEGG

IntegrationIntegration

Interface and OutputInterface and Output

Chaudhari and Li., BMC Research Notes, 2015, submitted.

Panel Interface PyMol 3D visualization Output Directory

Case StudyCase Study

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

CADD ResultsCADD Results

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