On the simulated scaling based free energy simulations: Adaptive optimization of the scaling parameter intervals

Abstract

Recently, we developed a generalized ensemble based free energy simulation technique, the simulated scaling (SS) method [Li et al., J. Chem. Phys. 126, 024106 (2007)]. In the SS simulations, random walks in the scaling parameter space are realized and free energy values can be conveniently estimated based on trial biasing weights. To improve free energy convergence in the SS simulations, we adopt a recent adaptive algorithm to systematically optimize the scaling parameter intervals; here, the optimization target is the round-trip rate between two end chemical states. As demonstrated in our model studies on the solvation of chloride ion and methane, free energy convergence can be greatly improved when the round-trip rates are accelerated.