APPLICATIONS OF FREE-ENERGY DERIVATIVES TO ANALOG DESIGN

Free energy derivatives, which were first used to analyze the sensitiv ity and the convergence of free energy calculations, have recently bee n proposed for use in analog design. In this article, we review the pu blished applications of free energy derivatives to analog design, disc uss the possible reasons for the success and failure of such applicati ons, and describe our recent study on an alternative use of free energ y derivatives in analog design. It is too early to definitively evalua te the usefulness of the free energy derivative method to yield valuab le insights into analog design. Our recent study suggests that free en ergy derivatives hold promise in evaluating possible different binding sites for a given ligand and suggesting the sites of a ligand that ar e not suitable for further structural modifications.