Free energy landscape for the binding process of Huperzine A to acetylcholinesterase.

ABSTRACT: Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, k(off) and activation free energy of dissociation (ΔG(off)≠). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzh

SUBMITTER: Bai F 

PROVIDER: S-EPMC3600462 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature