University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Ajay N. Jain, PhD

Ajay N. Jain, PhD

Professor, Department of Bioengineering and Therapeutic Science, UCSF

Cancer Center Program Memberships

Non-aligned

Research Summary

My research and training efforts are geared toward applications of computation to drug discovery, with an emphasis on making use of multiple methods and data types, exploiting synergy between protein structural data, chemical/target annotation information, and ligand binding affinity data. My laboratory has a particular focus on cancer-related therapeutic discovery, as are part of many collaborators that make use of our computational methods.

I have been at the forefront of computer-aided drug discovery (CADD) since the early 1990's, beginning in biotechnology start-ups such as Arris Pharmaceutical and continuing for over 20 years at UCSF. The central areas of research in the lab are: (1) methods for docking small molecules to proteins using empirically derived scoring functions; (2) methods for inducing the shape of a protein binding pocket given the structures and affinities of ligands that bind the pocket competitively; (3) generalized surface-based approaches to computing molecular similarity, both among small molecules and among proteins; and (4) approaches for very fast conformational search, including macrocycles, optionally including context from NMR restraints or fitting X-ray density maps. All of the approaches share their roots in the use of sophisticated computational algorithms involving object representation, function optimization, and search. My formal training at the PhD-level in Computer Science has been a distinct advantage in this work.

The following highlight recent work that is particularly relevant to the themes within the lab: synergy of diverse methods and data types for drug discovery. (1) We made use of a fast generalization of our ligand-based similarity approach (looking at small molecule surfaces from the outside) to instead quantify the similarity of protein binding sites (by looking at binding cavities from the inside). This approach (called PSIM) was shown to support characterization of proteins of unknown function. Using PSIM combined with other data, we developed hybrid approaches for (2) ligand affinity prediction, (3) prediction of polypharmacology, and (4) bioactive small molecule pose prediction.

Education

University of Minnesota, St. Paul, MN, BS, 1986, Biochemistry
University of Minnesota, Minneapolis, MN, BS, 1986, Computer Science
Carnegie Mellon University, Pittsburgh, PA, MS, 1989, Computer Science
Carnegie Mellon University, Pittsburgh, PA, PhD, 1991, Computer Science

Honors & Awards

  • 2010
    Levinthal Lecturer, Eleventh International CUP Symposium in Molecular Modeling

Selected Publications

  1. Sonkar C, Verma T, Chatterji D, Jain AK, Jha HC. Status of kinases in Epstein-Barr virus and Helicobacter pylori Coinfection in gastric Cancer cells. BMC Cancer. 2020 Sep 29; 20(1):925.
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  2. Jain AN, Cleves AE, Brueckner AC, Lesburg CA, Deng Q, Sherer EC, Reibarkh MY. XGen: Real-Space Fitting of Complex Ligand Conformational Ensembles to X-ray Electron Density Maps. J Med Chem. 2020 Sep 14.
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  3. Choudry FA, Hamshere SM, Rathod KS, Akhtar MM, Archbold RA, Guttmann OP, Woldman S, Jain AK, Knight CJ, Baumbach A, Mathur A, Jones DA. High Thrombus Burden in Patients With COVID-19 Presenting With ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2020 09 08; 76(10):1168-1176.
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  4. Panoulas V, Rathod KS, Jain AK, Firoozi S, Nevett J, Kalra SS, Malik IS, Mathur A, Redwood S, MacCarthy PA, Wragg A, Jones DA, Dalby MC. Impact of early (=24 h) versus delayed (>24 h) intervention in patients with non-ST segment elevation myocardial infarction: An observational study of 20,882 patients from the London Heart Attack Group. Cardiovasc Revasc Med. 2020 Jun 03.
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  5. Rathod KS, Beirne AM, Bogle R, Firoozi S, Lim P, Hill J, Dalby MC, Jain AK, Malik IS, Mathur A, Kalra SS, DeSilva R, Redwood S, MacCarthy PA, Wragg A, Smith EJ, Jones DA. Prior Coronary Artery Bypass Graft Surgery and Outcome After Percutaneous Coronary Intervention: An Observational Study From the Pan-London Percutaneous Coronary Intervention Registry. J Am Heart Assoc. 2020 Jun 16; 9(12):e014409.
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  6. Guzman M, Manithody C, Krebs J, Denton C, Besmer S, Rajalakshmi P, Jain S, Villalona GA, Jain AK. Impaired Gut-Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury. Nutrients. 2020 May 20; 12(5).
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  7. Cleves AE, Jain AN. Structure- and Ligand-Based Virtual Screening on DUD-E+: Performance Dependence on Approximations to the Binding Pocket. J Chem Inf Model. 2020 Apr 21.
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  8. Rathod KS, Jain AK, Firoozi S, Lim P, Boyle R, Nevett J, Dalby MC, Kalra S, Malik IS, Sirker A, Mathur A, Redwood S, MacCarthy PA, Wragg A, Jones DA. Outcome of inter-hospital transfer versus direct admission for primary percutaneous coronary intervention: An observational study of 25,315 patients with ST-elevation myocardial infarction from the London Heart Attack Group. Eur Heart J Acute Cardiovasc Care. 2020 Mar 20; 2048872619882340.
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  9. Cleves AE, Johnson SR, Jain AN. Electrostatic-field and surface-shape similarity for virtual screening and pose prediction. J Comput Aided Mol Des. 2019 10; 33(10):865-886.
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  10. Farmakis SG, Buchanan PM, Guzman MA, Hardy AK, Jain AK, Teckman JH. Shear wave elastography correlates with liver fibrosis scores in pediatric patients with liver disease. Pediatr Radiol. 2019 12; 49(13):1742-1753.
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  11. Jones DA, Rathod KS, Koganti S, Lim P, Firoozi S, Bogle R, Jain AK, MacCarthy PA, Dalby MC, Malik IS, Mathur A, DeSilva R, Rakhit R, Kalra SS, Redwood S, Ludman P, Wragg A. The association between the public reporting of individual operator outcomes with patient profiles, procedural management, and mortality after percutaneous coronary intervention: an observational study from the Pan-London PCI (BCIS) Registry using an interrupted time series analysis. Eur Heart J. 2019 08 14; 40(31):2620-2629.
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  12. Rathod KS, Koganti S, Jain AK, Rakhit R, Dalby MC, Lockie T, Kalra S, Malik IS, Knight CJ, Whitbread M, Mathur A, Firoozi S, Bogle R, Redwood S, MacCarthy PA, Sirker A, O'Mahony C, Wragg A, Jones DA. Complete Versus Culprit only Revascularisation in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction: Incidence and Outcomes from the London Heart Attack Group. Cardiovasc Revasc Med. 2020 Mar; 21(3):350-358.
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  13. Jain AN, Cleves AE, Gao Q, Wang X, Liu Y, Sherer EC, Reibarkh MY. Complex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen. J Comput Aided Mol Des. 2019 06; 33(6):531-558.
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  14. Rathod KS, Koganti S, Jain AK, Astroulakis Z, Lim P, Rakhit R, Kalra SS, Dalby MC, O'Mahony C, Malik IS, Knight CJ, Mathur A, Redwood S, Sirker A, MacCarthy PA, Smith EJ, Wragg A, Jones DA. Complete Versus Culprit-Only Lesion Intervention in Patients With Acute Coronary Syndromes. J Am Coll Cardiol. 2018 10 23; 72(17):1989-1999.
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  15. Antoniou S, Colicchia M, Guttmann OP, Rathod KS, Wright P, Fhadil S, Knight CJ, Jain AK, Smith EJ, Mathur A, Weerackody R, Wragg A, Jones DA. Risk scoring to guide antiplatelet therapy post-percutaneous coronary intervention for acute coronary syndrome results in improved clinical outcomes. Eur Heart J Qual Care Clin Outcomes. 2018 10 01; 4(4):283-289.
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  16. Denton C, Price A, Friend J, Manithody C, Blomenkamp K, Westrich M, Kakarla V, Phillips W, Krebs J, Abraham Munoz S, Osei H, Jain AK. Role of the Gut?Liver Axis in Driving Parenteral Nutrition-Associated Injury. Children (Basel). 2018 Sep 25; 5(10).
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  17. Cleves AE, Jain AN. Quantitative surface field analysis: learning causal models to predict ligand binding affinity and pose. J Comput Aided Mol Des. 2018 07; 32(7):731-757.
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  18. Rathod KS, Koganti S, Iqbal MB, Jain AK, Kalra SS, Astroulakis Z, Lim P, Rakhit R, Dalby MC, Lockie T, Malik IS, Knight CJ, Whitbread M, Mathur A, Redwood S, MacCarthy PA, Sirker A, O'Mahony C, Wragg A, Jones DA. Contemporary trends in cardiogenic shock: Incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group. Eur Heart J Acute Cardiovasc Care. 2018 Feb; 7(1):16-27.
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  19. Cleves AE, Jain AN. ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs. J Comput Aided Mol Des. 2017 May; 31(5):419-439.
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  20. Rathod KS, Jones DA, Van-Eijl TJ, Tsang H, Warren H, Hamshere SM, Kapil V, Jain AK, Deaner A, Poulter N, Caulfield MJ, Mathur A, Ahluwalia A. Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study. BMJ Open. 2016 12 20; 6(12):e012728.
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