Dr. Philip E. Bourne: Structural Bioinformatics & Systems Pharmacology

Research Summary: Network Pharmacology, Evolution and Scholarly Communication

Our laboratory focuses on three fundamental questions. (1) What happens when you take a drug? Recent research has focused on polypharmacology and finding off-target binding sites for major pharmaceuticals and new chemical entities to better understand possible side effects and opportunities for repositioning these compounds. At the heart of our work are new and efficient algorithms for ligand binding site searching, which have established the possible cause of side effects of a class of drugs known as Select Estrogen Receptor Modulators (SERMs) that includes tamoxifen as well as a possible repositioning of COMT inhibitors to treat extreme drug resistant tuberculosis. At this time we are systematically analyzing a number of major pharmaceuticals. (2) What is the ancestoral history of protein structure? Protein structure is more conserved than protein sequence over long evolutionary timescales and reveals evolutionary relationships not see from sequence alone. We have exploited this to define a tree of life based on protein structure information, established that life was influenced by shifts in trace metal geochemistry in the ocean and most recently suggested the existence of two new type of proteosome and described events associated with the emergence of alternative splicing. Inherent in all our work with proteins are the development of new methods to study protein motion, protein-protein interactions, and protein-protein global and local comparison. We use these methods to study cell signaling and immunology. We maintain the RCSB Protein Data Bank as part of collaboration with Rutgers University. (3) Can we improve the way science is disseminated and comprehended? Our laboratory is an advocate of open access publishing to maximize the distribution and impact of science and we develop resources using video and the full text of articles to enhance the learning experience for K12 as well as professional scientists.

Academic Achievements

Education: BSc (1973), BSc (Hon) (1974), Ph.D. in Chemistry (1980) – The Flinders University of South Australia.

Awards and Honors: UCSD Connect Award for New Inventions (1996 & 1997); Elected Fellow, American Medical Informatics Association (2002); Sun Microsystems Convergence Award (2002); Flinders University Convocation Medal for Outstanding Achievement (2004); Benjamin Franklin Award (2009); Fellow of the AAAS (2010).

Leadership Experience: Co-founder & Editor in Chief, PLoS Computational Biology (2005-); President, International Society for Computational Biology (2002-4); Leader Bioinformatics Track, BMS Program (2007-).

Teaching

• Biological Data and Analysis Tools (PHAR/BIOM 201).
• Professional Development (PHAR/BIOM 221).
• Pharmacy Informatics (SPPS 205).

Key Contributions to Pharmaceutical Sciences

• Repositioning and off target prediction of major pharmaceuticals.
• Development and support of the RCSB Protein Data Bank, the world wide repository on the structure of biological macromolecule.
• Systems Pharmacology

Selected Recent Publications (from >280 peer-reviewed articles and books)

Xie et al. (2009). Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors, PLoS Comp. Biol. 5:e1000387.

Pharmacy Informatics P.H. Anderson, S.M. McGuinness & P.E. Bourne 2009 (Eds.) Taylor & Francis

P.E. Bourne et al. (2012) Novel Computational Approaches to Polypharmacology as a Means to Define Responses to Individual Drugs, Annu Rev Pharmacol Toxicol 52:361-379

Potential Collaborative Programs with the Pharmaceutical Industry

• Off target prediction.
• Effective use of the Protein Data Bank.