Research Interests: Theoretical
Department of Chemistry, Columbia University
New York, NY 10027
The research in my group is focused on the following major areas:
Development and application of novel methods for ab initio electronic structure calculations, including mixed quantum mechanics/molecular mechanics (QM/MM) methods;
Development of a new generation of molecular mechanics force fields, including explicit incorporation of polarizability;
Investigation and improvement of continuum treatments of aqueous solvation;
Computational models and algorithms for protein structure prediction;
Modeling of protein-active site chemistry using quantum chemical and QM/MM methods;
Electron transfer theory; and
Quantum chemical modeling of the interactions of small molecules with surfaces and nanostructures.
Projects typically include a combination of analytical theory, algorithm and software development, and applications of new methods to biology or materials science.
Some highlights of our recent research are as follows:
Shee, J ; Arthur, EJ; Zhang, SW; Reichman, DR; Friesner, RA. Phaseless Auxiliary-Field Quantum Monte Carlo on Graphical Processing Units. Journal Of Chemical Theory And Computation. 14, 8, 4109-4121. (2018) DOI: 10.1021/acs.jctc.8b00342
Abel, R.; Mondal, S.; Masse, C.; Greenwood, J.; Harriman, G.; Ashwell, M.A.; Bhat, S.; Wester, S.; Frye, L.; Kapeller, R.; Friesner, R.A. Accelerating drug discovery through tight integration of expert molecular design and predictive scoring,Current Opinion In Structural Biology (2017) 43, 38-44 DOI: 10.1016/j.sbi.2016.10.007
Clark, AJ; Gindin, T; Zhang, BS; Wang, LL; Abel, R; Murret, CS; Xu, F; Bao, A; Lu, NJ; Zhou, TQ; Kwong, PD.; Shapiro, L.; Honig, B; Friesner RA. Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1. Journal Of Molecular Biology. 429, 7, 930-947 (2017) DOI: 10.1016/j.jmb.2016.11.021
Jacobson, LD; Bochevarov, AD; Watson, MA; Hughes, TF; Rinaldo, D; Ehrlich, S; Steinbrecher, TB; Vaitheeswaran, S; Philipp, DM; Halls, MD; Friesner, RA. Automated Transition State Search and Its Application to Diverse Types of Organic Reactions. Journal Of Chemical Theory And Computation. 13, 11, 5780-5797 (2017) DOI: 10.1021/acs.jctc.7b00764
Harder, E., D. Wolfgang, J. Maple, S. Wu, M. Rboul, J.Y. Xiang, L. Wang, D. Lupyan, M.K. Dahlgren, J.L. Knight, J.W. Kaus, D.S. Cerutti, G. Krilov, W.L, Jorgensen, R. Abel, R.A. Friesner, OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins. Journal Of Chemical Theory And Computation, 12, 1, 281-296 (2016). PMID: 26584231
Murphy, R.B., M.P. Repansky, J.R. Greenwood, I. Tubert-Brohman, S. Jerome, R. Annabhimoju, N.A. Boyles, C.D. Schmitz, R. Abel, R. Farid, R.A. Friesner, WScore: A Flexible and Accurate Treatment of Explicit Water Molecules in Ligand-Receptor Docking. J. Med. Chem., 59, 9, 4364-4384 (2016). PMID: 27054459
Clark, A.J., R. Tiwary, K. Borrelli, S. Feng, E.B. Miller, R. Abel, R.A. Friesner, B.J. Berne, Prediction of Protein Ligand Binding Poses via a Combination of Induced Fit Docking and Metadynamics Simulations, J. chem. Theor. Comput. 12, 6, 2990-2998 (2016). PMID: 27145262
Wang, L., YJ. Wu, Y.Q. Deng, B. Kim, L. Pierce, G. Krilov, D. Lupyan, S. Robinson, M.K. Dahlgren, J. Greenwood, D.L. Romero, C. Masse, J.L. Knight, T. Steinbrecher, T. Beuming, W. Damm, E. Harder, W. Sherman, M. Brewer, R. Wester, M. Murcko, L. Frye, R. Farid, T. Lin, D.L Mobley, W.L. Jorgensen, B.J. Berne, R.A. Friesner, R. Abel, Robert, Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field, J. Am. Chem. Soc., 137, 7, 2695-2703 (2015). PMID: 25625324
Miller, Edward B., Colleen S. Murrett, Kai Zhu, Suwen Zhao, Dahlia A. Goldfeld, Joseph H. Bylund, and Richard A. Friesner, Prediction of Long Loops with Embedded Secondary Structure using the Protein Local Optimization Program, J. Chem. Theo. Comput., 9, 1846-1864 (2013).
Hughes, Thomas F., and Richard A. Friesner, Development of Accurate DFT Methods for Computing Redox Potentials of Transition Metal Complexes: Results for Model Complexes and Application to Cytochrome P450, J. Chem. Theor. and Comput., 8, 442-459 (2012) DOE