Using multistate free energy techniques to improve the efficiency of replica exchange accelerated molecular dynamics.
Replica exchange accelerated molecular dynamics (REXAMD) is a method that enhances conformational sampling while retaining at least one replica on the original potential, thus avoiding the statistical problems of exponential reweighting. In this article, we study three methods that can combine the data from the accelerated replicas to enhance the estimate of properties on the original potential: weighted histogram analysis method (WHAM), pairwise multistate Bennett acceptance ratio (PBAR), and multistate Bennett acceptance ratio (MBAR). We show that the method that makes the most efficient use of equilibrium data from REXAMD simulations is the MBAR method. This observation holds for both alchemical free energy and structural observable prediction. The combination of REXAMD and MBAR should allow for more efficient scaling of the REXAMD method to larger biopolymer systems.
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0365, USA. mfajer@gmail.com
Mikolai
M
Fajer
Robert V
RV
Swift
J Andrew
JA
McCammon
D002073:Butanes / Q000737:chemistry; D003198:Computer Simulation; D008956:Models, Chemical; D008968:Molecular Conformation; D013816:Thermodynamics
D002073:Butanes; C046888:butane