Nagarajan Vaidehi, Ph.D.
Chair, Department of Computational and Quantitative Medicine
Research Area
Developing physics-based computational methods to study protein structure, dynamics and drug design
Appointments
Associate Director for Informatics and Computational Biomedicine, Comprehensive Cancer Center
Research Teams
Nagarajan Vaidehi, Ph.D., is professor and chair of the Department of Computational and Quantitative Medicine within Beckman Research Institute of City of Hope. Dr. Vaidehi also oversees the Computational Therapeutics Core.
Dr. Vaidehi received her Ph.D. in quantum chemistry from the Indian Institute of Technology in India, where she was honored with the Distinguished Alumni Award in 2016. Following her postdoctoral studies on protein dynamics simulation methods with Nobel Laureate Arieh Warshel, Ph.D., at University of Southern California, and William A Goddard III, Ph.D., at Caltech, she became the director of biomolecular simulations at the Materials and Process Simulation Center, Beckman Institute at Caltech.
Dr. Vaidehi joined City of Hope in 2006 as a professor and has since advanced the use of computational methods to meet the challenges of designing therapeutics. She is an internationally recognized biophysicist for her contributions in developing constrained molecular dynamics simulation methods with emphasis on application to G-protein coupled receptors and drug design.
1986, Indian Institute of Technology, Ph.D., Theoretical Chemistry
1981, Indian Institute of Technology, M.Sc., Chemistry (minor- Physics and Mathematics), Highest Honors
1991-1994, Postdoctoral Fellow at Caltech
1990-1991, Postdoctoral Fellow, University of Southern California, Prof. A. Warshel
1989-1990, Postdoctoral fellow at University of Exeter, U.K.
2020-present, Associate Director for Informatics and Computational Biomedicine, Comprehensive Cancer Center, City of Hope, Duarte, CA
2020-present, Professor, Department of Immunology & Theranostics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA
2018-present, Professor and Chair, Department Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, CA
2018-2020, Professor, Department of Molecular Imaging & Therapy, Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA
2005-2018, Professor, Department of Molecular Immunology, Beckman Research Institute of City of Hope, Duarte, CA
1998-2005, Director of Biosimulations, Materials and Process Simulation Center, Caltech, Pasadena, CA
1994-1998, Senior Scientist, Materials and Process Simulation Center, Caltech, Pasadena, CA
Selected Publications
Please refer to Pubmed for a detailed listing.
- Suno R, Lee S, Maeda S, Yasuda S, Yamashita K, Hirata K, Horita S, Tawaramoto MS, Tsujimoto H, Murata T, Kinoshita M, Yamamoto M, Kobilka BK, Vaidehi N, Iwata S, Kobayashi T. Structural insights into the subtype-selective antagonist binding to the M2 muscarinic receptor. Nat Chem Biol. 2018 Nov 12. doi: 10.1038/s41589-018-0152-y. [Epub ahead of print]
- Ghosh S, Bierig T, Lee S, Jana S, Löhle A, Schnapp G, Tautermann CS, Vaidehi N. Engineering Salt Bridge Networks between Transmembrane Helices Confers Thermostability in G-Protein-Coupled Receptors. J Chem Theory Comput. 2018 Nov 6. doi: 10.1021/acs.jctc.8b00602. [Epub ahead of print]
- Ma N, Lippert LG, Devamani T, Levy B, Lee S, Sandhu M, Vaidehi N, Sivaramakrishnan S. Bitopic Inhibition of ATP and Substrate Binding in Ser/Thr Kinases through a Conserved Allosteric Mechanism. Biochemistry. 2018 Nov 13;57(45):6387-6390. doi: 10.1021/acs.biochem.8b00729. Epub 2018 Oct 30.
- Tautermann CS, Binder F, Büttner FH, Eickmeier C, Fiegen D, Gross U, Grundl MA, Heilker R, Hobson S, Hoerer S, Luippold A, Mack V, Montel F, Peters S, Bhattacharya S, Vaidehi N, Schnapp G, Thamm S, Zeeb M. Allosteric Activation of Striatal-Enriched Protein Tyrosine Phosphatase (STEP, PTPN5) by a Fragment-like Molecule. J Med Chem. 2018 Sep 12. doi: 10.1021/acs.jmedchem.8b00857. [Epub ahead of print]
- Bhargava R, Sandhu M, Muk S, Lee G, Vaidehi N, Stark JM. C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains. Nat Commun. 2018 Jun 27;9(1):2484. doi: 10.1038/s41467-018-04867-5.
- Nivedha AK, Tautermann CS, Bhattacharya S, Lee S, Casarosa P, Kollak I, Kiechle T, Vaidehi N. Identifying Functional Hotspot Residues for Biased Ligand Design in G-Protein-Coupled Receptors. Mol Pharmacol. 2018 Apr;93(4):288-296. doi: 10.1124/mol.117.110395. Epub 2018 Jan 24.
- Li H, Sandhu M, Malkas LH, Hickey RJ, Vaidehi N. How Does the Proliferating Cell Nuclear Antigen Modulate Binding Specificity to Multiple Partner Proteins? J Chem Inf Model. 2017 Dec 26;57(12):3011-3021. doi: 10.1021/acs.jcim.7b00171. Epub 2017 Nov 17.
- Lee S, Devamani T, Song HD, Sandhu M, Larsen A, Sommese R, Jain A, Vaidehi N, Sivaramakrishnan S. Distinct structural mechanisms determine substrate affinity and kinase activity of protein kinase Cα. J Biol Chem. 2017 Sep 29;292(39):16300-16309. doi: 10.1074/jbc.M117.804781. Epub 2017 Aug 15.
- Choy C, Ansari KI, Neman J, Hsu S, Duenas MJ, Li H, Vaidehi N, Jandial R. Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases. Breast Cancer Res. 2017 Apr 26;19(1):51. doi: 10.1186/s13058-017-0844-3.
- Krumm BE, Lee S, Bhattacharya S, Botos I, White CF, Du H, Vaidehi N, Grisshammer R. Structure and dynamics of a constitutively active neurotensin receptor. Sci Rep. 2016 Dec 7;6:38564. doi: 10.1038/srep38564.
- Lee S, Mao A, Bhattacharya S, Robertson N, Grisshammer R, Tate CG, Vaidehi N. How Do Short Chain Nonionic Detergents Destabilize G-Protein-Coupled Receptors? J Am Chem Soc. 2016 Nov 30;138(47):15425-15433. Epub 2016 Nov 15.
- Vaidehi N, Bhattacharya S. Allosteric communication pipelines in G-protein-coupled receptors. Curr Opin Pharmacol. 2016 Oct;30:76-83. doi: 10.1016/j.coph.2016.07.010. Epub 2016 Aug 4. Review.
- Bhattacharya S, Salomon-Ferrer R, Lee S, Vaidehi N. Conserved Mechanism of Conformational Stability and Dynamics in G-Protein-Coupled Receptors. J Chem Theory Comput. 2016 Nov 8;12(11):5575-5584. Epub 2016 Oct 17.
- Semack A, Sandhu M, Malik RU, Vaidehi N, Sivaramakrishnan S. Structural Elements in the Gαs and Gαq C Termini That Mediate Selective G Protein-coupled Receptor (GPCR) Signaling. J Biol Chem. 2016 Aug 19;291(34):17929-40. doi: 10.1074/jbc.M116.735720. Epub 2016 Jun 21.
- Kandel S, Salomon-Ferrer R, Larsen AB, Jain A, Vaidehi N. Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations. J Chem Phys. 2016 Jan 28;144(4):044112. doi: 10.1063/1.4939532.
- Vaidehi N, Grisshammer R, Tate CG. How Can Mutations Thermostabilize G-Protein-Coupled Receptors? Trends Pharmacol Sci. 2016 Jan;37(1):37-46. doi: 10.1016/j.tips.2015.09.005. Epub 2015 Nov 5. Review.
- Soto AG, Smith TH, Chen B, Bhattacharya S, Cordova IC, Kenakin T, Vaidehi N, Trejo J. N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias. Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):E3600-8. doi: 10.1073/pnas.1508838112. Epub 2015 Jun 22.
- Lee S, Heinrich EL, Li L, Lu J, Choi AH, Levy RA, Wagner JE, Yip ML, Vaidehi N, Kim J. CCR9-mediated signaling through β-catenin and identification of a novel CCR9 antagonist. Mol Oncol. 2015 Oct;9(8):1599-611. doi: 10.1016/j.molonc.2015.04.012. Epub 2015 May 12.
- Lee S, Bhattacharya S, Tate CG, Grisshammer R, Vaidehi N. Structural dynamics and thermostabilization of neurotensin receptor 1. J Phys Chem B. 2015 Apr 16;119(15):4917-28. doi: 10.1021/jp510735f. Epub 2015 Apr 7.
- Yu DD, Sousa KM, Mattern DL, Wagner J, Fu X, Vaidehi N, Forman BM, Huang W. Stereoselective synthesis, biological evaluation, and modeling of novel bile acid-derived G-protein coupled bile acid receptor 1 (GP-BAR1, TGR5) agonists. Bioorg Med Chem. 2015 Apr 1;23(7):1613-28. doi: 10.1016/j.bmc.2015.01.048. Epub 2015 Feb 11.