Dr. Ruben Abagyan

Protein Modeling and Docking, Drug and Target Discovery, Adverse Effects, New Therapies

abagyan
Ruben Abagyan, Ph.D.

Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences

Email
rabagyan@health.ucsd.edu
Phone
(858) 822-3404
Research Summary

Dr. Abagyan’s research focuses on the development of novel technologies for structure based drug discovery and optimization, structural systems biology for target finding and protein modeling. The lab screens specific biomedical targets to discover new drug leads, and validate them experimentally. The applications include cancer, neurodegeneration, parasitic, viral and endocrine diseases. To extend the reach of docking we model alternative functional states and allosteric pockets of the kinases, GPCRs and Nuclear Receptors. We derived comprehensive sets of ligand pockets (the Pocketome) competing for ligands and metabolites in different organisms. These data are used for target identification and multi-target pharmacology profiling. We dock drugs, leads and environmental chemicals to the ‘anti-target’ models to predict endocrine disruption and other adverse effects. We also identify new promising uses of existing drugs on the basis of the multi-target pharmacology.

Academic Achievements

Education: S.c. laude M.S. in Molecular and Chemical Biophysics (1980) Moscow Inst. Physics & Technology; Ph.D. in Protein Structure Prediction (1984) Moscow State University. 

Awards and Honors: Two CapCure awards for excellence in prostate cancer research (2000, 2002); Princess Diana award and medal, Sydney (2003); UCSD Faculty and Staff Excellence Award (2007).  AACP’s 2016 Teacher of the Year Award; SSPPS Student-voted Faculty of the Year Award (2018). Recognition as top 1% most performing and cited faculty, https://hcr.clarivate.com/ (2018).

Leadership Experience: Director of Computational Biology & IT at Skirball Inst. of Biomolecular Medicine, New York (1994-1999); Director at Novartis Institute, GNF (1999-2002); SBDD chair, MipTec, Basel, Switzerland (2002-2009); Founder of MolSoft (1994); Member of Board of Directors of Syrrx (2001-2002); SAB Member of Plexus Vaccines (2001- 2003); Editorial Boards (current): Endocrine Disruptors, Am.J.Pharm.Tox, Cancer Genomics and proteomics, IUPAC Glossary Committee, J.Comp- Aided Mol.Des.; Steering Committee member of UCSD Bioinformatics and Systems Biology Graduate Program, the Swiss NSF NCCR- Transcure Center, and Hong Kong PolyU State Key Laboratory and Steering, Review or Advisory panel member. European Research Council Synergy Review Panel (2018,2019,2022)

Teaching
  • Pharmaceutical Chemistry II, Physical Pharmacology (SPPS 222)
  • Principles of Pharmaceutical Sciences and Drug Development (SPPS 263A)
Key Contributions
  • Internal Coordinate Mechanics (ICM) for structure sampling, dynamics, molecular docking.
  • Stochastic global optimization method with collective (fragment) moves, square-root sampling.
  • Ligand Guided homology modeling. Structure-based lead discovery for many molecular targets.
  • The Pocketome for target profiling and pharmacology prediction of leads and drugs
Selected Publications

(view more)

Potential Collaborative Programs
  • In silico screening of billions of compounds for binders to a molecular target, structure-based lead discovery and optimization, finding covalent or non-covalent inhibitors with a particular multi-target profile. Current therapeutic areas: oncology, neurodegenerative, psychiatric and neurological diseases, autoimmune disease, viral, bacterial, or eukaryotic parasitic infectious pathogens
  • Finding molecular targets of an active compound by docking to Pocketome-encyclopedia
  • Machine-learning models for pharmacological outcomes and molecular targets, predicting multi-target pharmacology and adverse effects of drugs and environmental chemicals