Speaker: Dr. Mark E. Tuckerman
From: Department of Chemistry and Courant Institute of Mathematical Sciences -
New York University - New York, NY
Date / Time / Room: Friday, April 22, 2005 / 3:30 - 4:30 PM/Room 127 Hayes Healy

Title: Enhanced conformational sampling via novel variable transformations and adiabatic dynamics: Applications to small polypeptides, model proteins and drug binding in the HIV-1 protease

Abstract: One of the computational grand challenge problems is the development of methodology capable of sampling conformational equilibria in systems with rough energy landscapes. If met, many important problems, most notably protein folding, could be signi€cantly im¬pacted. In this talk, I will present a new approach in which molecular dynamics is combined with a novel variable transformation designed to warp con€guration space in such a way that barriers are reduced and attractive basins stretched. The new method rigorously preserves equilibrium properties while leading to very large enhancements in sampling efficiency. The new approach is used to investigate the folding of a model ? -barrel protein. Moreover, when variable transformations are combined with an adiabatic separation between a reactive sub¬space of coordinates and the remaining degrees of freedom, an efficient method for exploring free energy surfaces emerges. These new methods are applied to study the conformational equilibria of small polypeptides and complexes of the HIV-1 protease with fullerene-derived inhibitors. In the latter example, a possible mechanism for increasing the binding affinity in the active site of the HIV-1 protease is revealed.