Optimization of Umbrella Sampling Replica Exchange Molecular Dynamics by Replica Positioning.

Abstract

The positioning of sampling windows in an umbrella sampling simulation has an effect on the rate of convergence and computational efficiency. When such simulation is coupled with a Hamiltonian replica exchange setup, we show that such positioning can be optimized for maximal convergence of the results. We present a method for estimating the exchange acceptance ratio (EAR) between two arbitrary positions on a reaction coordinate in umbrella sampling replica exchange (USRE) molecular dynamics (MD). We designed a scoring function to optimize the position of the set of replicas (windows). By maximizing the scoring function, we make EAR the same for all neighbor replica pairs, increasing the efficiency of the method. We tested our algorithm by sampling a torsion for butane in implicit solvent and by studying a salt bridge in explicit solvent. We found that the optimized set of replicas recovers the correct free energy profile much faster than for equally spaced umbrellas.