LIGAND-BINDING AFFINITY PREDICTION BY LINEAR INTERACTION ENERGY METHODS

A recent method for estimating ligand binding affinities is extended. This method employs averages of interaction potential energy terms fro m molecular dynamics simulations Ir other thermal conformational sampl ing techniques. Incorporation of systematic deviations from electrosta tic linear response, derived from free energy perturbation studies, in to the absolute binding free energy expression significantly enhances the accuracy of the approach. This type of method may be useful for co mputational prediction of ligand binding strengths, e.g., in drug desi gn applications.