A new method for predicting binding affinity in computer-aided drug design

Abstract

A new semi-empirical method for calculating free energies of binding from molecular dynamics (MD) simulations is presented. It is based on standard thermodynamic cycles and on a linear approximation of polar and non-polar free energy contributions from the corresponding MD averages. The method is tested on a set of endothiapepsin inhibitors and found to give accurate results both for absolute as well as relative free energies.