LAMBDA-DYNAMICS - A NEW APPROACH TO FREE-ENERGY CALCULATIONS

We present a novel and efficient method for performing free energy cal culations. Treating the conventional lambda variables associated with the ''progress'' in the chemical coordinates dynamically, our approach transforms free energy calculations into calculating potentials of me an force in the lambda-space with molecular dynamics. This extended Ha miltonian formalism utilizes the full power of umbrella sampling techn iques and the weighted histogram analysis method. Applications to free energies of hydration and a model illustrating competitive binding ca lculations are presented. These calculations demonstrate the robustnes s and flexibility of the new lambda-dynamics approach. (C) 1996 Americ an Institute of Physics.