Exploring Protocols to Build Reservoirs to Accelerate Temperature Replica Exchange MD Simulations.

Abstract

Temperature replica exchange molecular dynamics (REMD) is a widely used enhanced sampling method for accelerating biomolecular simulations. During the past 2 decades, several variants of REMD have been developed to further improve the rate of conformational sampling of REMD. One such variant, reservoir REMD (RREMD), was shown to improve the rate of conformational sampling by around 5-20×. Despite the significant increase in the sampling speed, RREMD methods have not been widely used because of the difficulties in building the reservoir and also because of the code not being available on the graphics processing units (GPUs). In this work, we ported the Amber RREMD code onto GPUs making it 20× faster than the central processing unit code. Then, we explored protocols for building Boltzmann-weighted reservoirs as well as non-Boltzmann reservoirs and tested how each choice affects the accuracy of the resulting RREMD simulations. We show that, using the recommended protocols outlined here, RREMD simulations can accurately reproduce Boltzmann-weighted ensembles obtained by much more expensive conventional temperature-based REMD simulations, with at least 15× faster convergence rates even for larger proteins (>50 amino acids) compared to conventional REMD.