Exploring Energy and Fitness Landscapes of Proteins

Ronald M. Levy Center for Biophysics and Computational Biology & Department of Chemistry, Temple University, Philadelphia, PA

My talk will review work in my lab over the last several years concerning the construction and analysis of energy and fitness landscapes for protein-ligand binding and allosteric transitions. I will discuss both structure based approaches which employ molecular dynamics simulations and sequence based approaches which employ Potts models. Examples will be chosen from HIV family proteins and Kinase family proteins.

References [1] Gallicchio, E., and R.M. Levy. Advances in all atom sampling methods for modeling protein-ligand binding affinities. Current Opinion in Structural Biology, 21 , 161-166 (2011)

[2] Deng, N., W. Zheng, E. Gallicchio, and R.M. Levy. Insights into the Dynamics of HIV-1 Protease: a Kinetic Network Model Constructed from Atomistic Simulations, J. Am. Chem. Soc., 133, 9387-9394 (2011)

[3] Gallicchio, E., N. Deng, P. He, A.L. Perryman, D.N. Santiago, S. Forli, A.J. Olson, R.M. Levy. Virtual Screening of Integrase Inhibitors by Large Scale Binding Free Energy Calculations. J. Comp. Aided. Mol. Design, DOI 10.1007/s10822-014-9711-9 (2014)

[4] Vijayan, R. S. K., Peng He, Vivek Modi, Krisna C. Duong-Ly, Haiching Ma, Jeffrey R. Peterson, Roland L. Dunbrack, and Ronald M. Levy. Conformational Analysis of the DFG-Out Kinase Motif and Biochemical Profiling of Structurally Validated Type II Inhibitors Journal of Medicinal Chemistry, 58, 466-479 (2015)

[5] Haq, Omar, Michael Andrec, Alexandre V. Morozov, and Ronald M. Levy. Correlated Electrostatic Mutations Provide a Reservoir of Stability in HIV Protease PLoS Computational Biology, 8, e1002675. PMCID: PMC3435258 (2012).