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

Ajay N. Jain, PhD

Professor, Departments of Biopharmaceutical Sciences and Laboratory Medicine, UCSF

Cancer Center Program Memberships


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 the past 16 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 modeling and prediction of polypharmacology based on molecular structure. 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.


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

Professional Experience

  • 1983-1986
    Research Engineer, Machine Vision Technology, Honeywell, Minneapolis, MN
  • 1992
    Principal Research Scientist, Multi-Sensor Signal Processing. Alliant Techsystems (formerly Honeywell), Minneapolis, MN
  • 1992-1996
    Senior Scientist and Group Leader of Computational Sciences, Arris Pharmaceutical, So. San Francisco, CA
  • 1996-1997
    Principal Scientist and Group Leader of Computational Sciences, MetaXen LLC, Hayward, CA
  • 1997-present
    Founder and Chief Scientist, BioPharmics, San Mateo, CA
  • 1998-1999
    Director of Applied Computing, Iconix Pharmaceuticals, Mountain View, CA
  • 1999-present
    Full Member, UCSF Cancer Center, University of California, San Francisco, CA
  • 1999-2002
    Director of Informatics, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
  • 1999-2002
    Associate Adjunct Professor, Cancer Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA
  • 2002-present
    Director, Informatics Core, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
  • 2002-2007
    Associate Professor, Cancer Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA
  • 2004-2007
    Associate Professor, Department of Biopharmaceutical Sciences, University of California, San Francisco, CA
  • 2007-present
    Professor, Cancer Research Institute, Department of Biopharmaceutical Sciences, and Department of Laboratory Medicine, University of California, San Francisco, CA

Honors & Awards

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

Selected Publications

  1. Ai H, Cao Y, Jain A, Wang X, Hu Z, Zhao G, Hu S, Shen X, Yan Y, Liu X, Sun Y, Lan X, Xu G, Sun S. The ferroxidase LPR5 functions in the maintenance of phosphate homeostasis and is required for normal growth and development of rice. J Exp Bot. 2020 Jul 03.
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  2. 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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  3. Sun Y, Jain A, Xue Y, Wang X, Zhao G, Liu L, Hu Z, Hu S, Shen X, Liu X, Ai H, Xu G, Sun S. OsSQD1 at the crossroads of phosphate and sulfur metabolism affects plant morphology and lipid composition in response to phosphate deprivation. Plant Cell Environ. 2020 Jul; 43(7):1669-1690.
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  4. Cao Y, Jain A, Ai H, Liu X, Wang X, Hu Z, Sun Y, Hu S, Shen X, Lan X, Xu G, Sun S. OsPDR2 mediates the regulation on the development response and maintenance of Pi homeostasis in rice. Plant Physiol Biochem. 2020 Apr; 149:1-10.
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  5. 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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  6. 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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  7. Pei W, Jain A, Ai H, Liu X, Feng B, Wang X, Sun Y, Xu G, Sun S. OsSIZ2 regulates nitrogen homeostasis and some of the reproductive traits in rice. J Plant Physiol. 2019 Jan; 232:51-60.
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  8. Jones DA, Rathod KS, Koganti S, Hamshere S, Astroulakis Z, Lim P, Sirker A, O'Mahony C, Jain AK, Knight CJ, Dalby MC, Malik IS, Mathur A, Rakhit R, Lockie T, Redwood S, MacCarthy PA, Desilva R, Weerackody R, Wragg A, Smith EJ, Bourantas CV. Angiography Alone Versus Angiography Plus Optical Coherence Tomography to Guide Percutaneous Coronary Intervention: Outcomes From the Pan-London PCI Cohort. JACC Cardiovasc Interv. 2018 07 23; 11(14):1313-1321.
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  9. 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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  10. Harlow KE, Africa JA, Wells A, Belt PH, Behling CA, Jain AK, Molleston JP, Newton KP, Rosenthal P, Vos MB, Xanthakos SA, Lavine JE, Schwimmer JB. Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease. J Pediatr. 2018 07; 198:76-83.e2.
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  11. 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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  12. Saxena M, Sobotka PA, Hamshere SM, Jain A, Mathur A, Knight C, Collier DJ, Lobo MD. Antihypertensive Effects of a Central Arteriovenous Anastomosis Are Mediated Through Profound Reduction in Systemic Vascular Resistance. Circ Cardiovasc Interv. 2016 08; 9(8):e004012.
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  13. Cleves AE, Jain AN. Extrapolative prediction using physically-based QSAR. J Comput Aided Mol Des. 2016 Feb; 30(2):127-52.
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  14. Cleves AE, Jain AN. Knowledge-guided docking: accurate prospective prediction of bound configurations of novel ligands using Surflex-Dock. J Comput Aided Mol Des. 2015 Jun; 29(6):485-509.
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  15. Rathod KS, Jones DA, Gallagher S, Rathod VS, Weerackody R, Jain AK, Mathur A, Mohiddin SA, Archbold RA, Wragg A, Knight CJ. Atypical risk factor profile and excellent long-term outcomes of young patients treated with primary percutaneous coronary intervention for ST-elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2016 Feb; 5(1):23-32.
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  16. Cleves AE, Jain AN. Chemical and protein structural basis for biological crosstalk between PPARa and COX enzymes. J Comput Aided Mol Des. 2015 Feb; 29(2):101-12.
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  17. Yera ER, Cleves AE, Jain AN. Prediction of off-target drug effects through data fusion. Pac Symp Biocomput. 2014; 160-71.
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  18. Spitzer R, Cleves AE, Varela R, Jain AN. Protein function annotation by local binding site surface similarity. Proteins. 2014 Apr; 82(4):679-94.
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  19. Varela R, Cleves AE, Spitzer R, Jain AN. A structure-guided approach for protein pocket modeling and affinity prediction. J Comput Aided Mol Des. 2013 Nov; 27(11):917-34.
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  20. Jain A, Poonia B, So EC, Vyzasatya R, Burch EE, Olsen HS, Mérigeon EY, Block DS, Zhang X, Schulze DH, Hanna NN, Twadell WS, Yfantis HG, Chan SL, Cai L, Strome SE. Tumour antigen targeted monoclonal antibodies incorporating a novel multimerisation domain significantly enhance antibody dependent cellular cytotoxicity against colon cancer. Eur J Cancer. 2013 Oct; 49(15):3344-52.
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