College of Liberal Arts & Sciences

Exploring Fitness and Free Energy Landscapes of Proteins

Tuesday, April 24, 2018

Exploring Fitness and Free Energy Landscapes of Proteins

Tuesday, April 24, 2018

1:00 p.m. Room 202 MRB

Ronald M. Levy

Professor Center for Biophysics and Computational Biology Institute for Computational Molecular Science Department of Chemistry Temple University Philadelphia, Pennsylvania

My talk will review recent work in in my lab concerning the construction and analysis of fitness and free energy landscapes of proteins. In the first part of my talk I will describe the Potts Hamiltonian statistical model of sequence co‐variation, and how we are using it to study the acquisition of drug resistance in HIV proteins. The likelihood of a mutation at one position in a genome depends on the pattern of mutations at all the other positions. This phenomenon is called epistasis, and it is responsible for the “entrenchment” of drug resistance mutations when a sufficient number of background mutations accumulate in the genome. I will also talk about our efforts to map the conformational free energy landscape of kinase family proteins, using the Potts model to infer sequence probabilities and their structural propensities, and to connect this information to conformational free energy simulations in structure space. In the second part of my talk I will describe recent work in my lab focused on free energy simulations of protein‐ligand binding, binding allostery, and the statistical thermodynamics of solvation at the interface. I will describe two alternative perspectives for predicting the effects on binding affinity of displacing structured waters at protein receptor binding sites when ligands bind. I will try to address the question, “What can statistical mechanics contribute to the drug design process?”



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