Dr. Chris Chipot
Nancy Université
Vandoeuvre-les-Nancy, France

Wednesday, September 5, 2012
3:00 pm (CT)
3269 Beckman Institute

Abstract

One of the current grand challenges of molecular modeling is the faithful description of the reaction coordinates that characterize processes of biological interest. Closely related to this endeavor, the determination of accurate free-energy changes along the model reaction coordinates constitutes an even greater challenge. Sampling the relevant degrees of freedom while circumventing hidden barriers will be illustrated in the challenging case of standard binding free energies, which represent not only a tangible, quantitative link between experiment and theory, but also a cogent test to discriminate between force-field related systematic errors and both conceptual and sampling issues. The choice of the best possible strategy, either perturbtive or gradient-based, alongside with its inherent limitations will be discussed and illustrated with the src-homology domain 3 of the Abl kinase interacting with an agonist peptide.