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Vsevolod Katritch, Ph.D.

Assistant Professor of Molecular Biology
Department of Integrative Structural and Computational Biology
California Campus
katritch@scripps.edu
(858) 784-7723

Research Focus

Dr. Katritch’s research is focused on development and application of 3D molecular modeling and bioinformatics tools to further understanding of structure and function of membrane proteins and specifically G protein-coupled receptors (GPCRs). The recent breakthroughs in the crystallography of the GPCR superfamily established a robust 3D structural platform for a synergistic combination of computational, biochemical and biophysical inquiries. The ongoing applications include (i) conformational modeling of receptor interactions with different classes of ligands (ii) iterative multi-template homology modeling  of GPCR subtypes (iii) technologies for ligand guided receptor optimization, with applications to structure-based virtual ligand screening and rational lead optimization, (iv) combining molecular modeling with biophysical (e.g. NMR, EPR, HDX) approaches to decipher details of GPCR activation mechanisms, and (v) studies of molecular interactions in downstream GPCR signaling, also in the context of systems biology of GPCR-mediated pathways. These studies involve close collaborations with crystallographers, biophysicists, molecular biologists, medicinal chemists and bioinformaticians at Scripps, UCSD, NIH and other institutions, ultimately aiming to explore new venues for structure-based rational drug discovery for GPCR targets.

Education

B.Sc., Physics and Applied Math,, Moscow Institute of Physics & Technology (MIPT), 1991
M.Sc., Biophysics & Mol. Biology, MIPT, 1993
Ph.D., Biophysics & Mol. Biology, MIPT, 1996

Selected References

  1. Tosh, D. K.; Phan, K.; Gao, Z. G.; Gakh, A. A.; Xu, F.; Deflorian, F.; Abagyan, R.; Stevens, R. C.; Jacobson, K. A.; Katritch, V. (2012) Optimization of Adenosine 5’-Carboxamide Derivatives as Adenosine Receptor Agonists Using Structure-Based Ligand Design and Fragment-Based Searching. J. Med. Chem., in press.
  2. Thompson, A. A.; Liu, W.; Chun, E.; Katritch, V.; Wu, H.; Vardy, E.; Huang, X. P.; Trapella, C.; Guerrini, R.; Calo, G.; Roth, B. L.; Cherezov, V.; Stevens, R.C. (2012) Structure of the Nociceptin/Orphanin FQ Receptor in Complex with a Peptide Mimetic. Nature , in press
  3. Wu, H.; Wacker, D.; Mileni, M.; Katritch, V.; Han, G. W.; Vardy, E.; Liu, W.; Thompson, A. A.; Huang, X. P.; Carroll, F. I.; Mascarella, S. W.; Westkaemper, R. B.; Mosier, P. D.; Roth, B. L.; Cherezov, V.; Stevens, R. C. (2012). Structure of the human kappa-opioid receptor in complex with JDTic. Nature, in press
  4. Liu, J. J.; Horst, R.; Katritch, V.; Stevens, R. C.; Wuthrich, K. (2012). Biased Signaling Pathways in beta2-Adrenergic Receptor Characterized by 19F-NMR. Science, 335, 1106-1110
  5. Katritch, V.; Rueda, M.; Abagyan, R. Ligand-guided receptor optimization. Methods Mol Biol 2012, 857, 189-205.
  6. Katritch, V. and R. Abagyan. GPCR agonist binding revealed by modeling and crystallography. (2011) Trends in Pharm. Sciences, 32(11):637-43.
  7. Katritch. V., Cherezov. V. and Stevens, R.C. (2012) Diversity and Modularity of G Protein-Coupled Receptor Structures. Trends in Pharm. Sciences, 33, 17-27
  8. Shimamura, T., Shiroishi, M., Weyand, S., Tsujimoto, H., Winter, G., Katritch, V., Abagyan, R., Cherezov, V., Liu, W., Han G.W., Kobayashi, T., Stevens R.C. and S. Iwata. (2011) Structure of the human histamine H1 receptor complex with doxepin. Nature, 475(7354):65-70.
  9. West, G.M., Chien, E.Y.T, Katritch, V., Gatchalian, J., Chalmers, M.J, Stevens. R.C and P.R. Griffin (2011). Ligand-dependent perturbation of the conformational ensemble of the GPCR beta2 adrenergic receptor revealed by HDX. Structure, 10.1016/j.str.2011.08.001.
  10. Kufareva, I., Rueda, M., Katritch, V., participants of GPCR Dock 2010, Stevens, R.C. and R. Abagyan. (2011). Status of GPCR modeling and docking as reflected by community wide GPCR Dock 2010 assessment. Structure 19(8):1108-26.
  11. Tiefenbrunn, T., Liu, W., Chen, Y., Katritch, V., Stout, C.D.,  Fee, J.A. and V. Cherezov (2011) High Resolution Structure of the ba3 Cytochrome c Oxidase from Thermus thermophilus in a Lipidic Environment. PLoS ONE. 6(7):e22348.
  12. Xu, F., Wu, H., Katritch, V., Han, G.W., Jacobson, K.A., Gao, Z.G., Cherezov, V. and R,C. Stevens. (2011) Structure of an agonist-bound human A2A adenosine receptor. Science, 332(6027):322-7
  13. Katritch, V., Kufareva, I. and R. Abagyan (2011). Structure based prediction of subtype-selectivity for adenosine receptor antagonists. Neuropharmacology 60(1):108-15.
  14. Chien,E.Y.T, Liu, W., Zhao, Q., Katritch, V., Han, G.W., Hanson, M.A., Shi, L., Newman, A.H., Javitch, J.A., Cherezov, V. and R.C. Stevens (2010). “Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist.” Science, 330(6007):1091-5. NIHMSID 247444
  15. Wu, B., Chien, E.Y.T., Mol, C.D., Fenalti, G., Liu, W., Katritch, V., Abagyan, R., Brooun, A., Wells, P., Bi, F.C., Hamel, D.J., Kuhn, P., Handel, T.M., Cherezov, V. and R.C. Stevens (2010) “Structures of the CXCR4 chemokine receptor in complex with small molecule and cyclic peptide antagonists.”  Science, 330(6007):1066-71.
  16. Rueda, M., Katritch, V., Raush, E. and R. Abagyan. (2010) “SimiCon: A web tool for protein-ligand model comparison through calculation of equivalent atomic contacts.” Bioinformatics, 26(21):2784-5.
  17. Wacker, D., Fenalti, G., Brown, M., Katritch, V., Abagyan, R., Cherezov, V. and R.C. Stevens (2010). “Conserved binding mode of human b2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography.”  JACS, 132(33):11443-5.
  18. Jaakola, V.P., Lane, R.J., Lin, J.Y., Katritch, V. IJzerman, A.P., and R.C. Stevens (2010). Ligand binding and subtype selectivity of the human A(2A) adenosine receptor: identification and characterization of essential amino acid residues. JBC, 285(17):13032-44 
  19. Katritch, V., Jaakola, V.P., Lane, J.R., Lin, J., IJzerman, A.P. Yeager, M., Kufareva, I., Stevens, R.C. and R. Abagyan (2010). Structure-Based Discovery of Novel Chemotypes for Adenosine A2A Receptor Antagonists, J. Med. Chem., 53(4):1799-809
  20. Reynolds, K. A., Katritch, V. and Abagyan, R. (2010) Structure and Modeling of GPCRs: Implications for Drug Discovery, in GPCR Molecular Pharmacology and Drug Targeting: Shifting Paradigms and New Directions (ed. A. Gilchrist), John Wiley & Sons, Inc., Hoboken, NJ, USA. pp. 385-433, doi: 10.1002/9780470627327.ch15.
  21. Katritch, V., Rueda, M. Lam, P. C. Yeager, M. and R. Abagyan. GPCR 3D Homology Models for Ligand Screening: Lessons Learned from Blind Predictions of Adenosine A2a Receptor complex. (2010) Proteins, 78(1):197-211. 
  22. Katritch, V., Cherezov, V., Hanson, M.A., Roth, R.B., Reynolds, K. A. and Abagyan, R. (2009). Analysis of the β2AR structure provides insight into agonist binding and the role of the transmembrane helix V in receptor activation. J Mol Recognit, 22(4):p.307-1
  23. Rynolds, K. A., Katritch, V., and Abagyan, R. (2009) Identifying conformational changes of b2 adrenoceptor that enable accurate prediction of ligand/receptor interactions and screening for GPCR modulators. J. Comp. Aided Mol Des, 23(5): p. 273-88.
  24. Cherezov, V., Liu, W., Derrick, J.P., Luan, B., Aksimentiev A., Katritch V. and Caffrey, M. (2008). "In meso Crystal Structure and Docking Simulations Suggest an Alternative Proteoglycan Binding Site in the OpcA Outer Membrane Adhesin". Proteins 71(1):24-34.
  25. Katritch, V., Byrd, C., Tseitin, V., Dai, D., Raush, E., Totrov, M., Abagyan., Jordan, R. and Hruby, D. (2007). Discovery of non-peptide inhibitors of ubiquitin-like poxvirus proteinase I7L using comparative protein modeling and covalent docking approach. J. Comp. Aided Mol. Design, 21, 549-58.

Links

GPCR Network