Using Multistate Free Energy Techniques to Improve the Efficiency of Replica Exchange Accelerated Molecular Dynamics

作者：Fajer Mikolai^*; Swift Robert V; McCammon J Andrew

来源：Journal of Computational Chemistry, 2009, 30(11): 1719-1725.

DOI：10.1002/jcc.21285

• molecular dynamics simulation
• replica exchange
• enhanced sampling
• free energy
• thermodynamics

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.

• 出版日期2009-8