Evaluationof Enhanced Sampling Provided by AcceleratedMolecular Dynamics with Hamiltonian Replica Exchange Methods

摘要

Many problems studied via molecular dynamics require accurate estimates of various thermodynamic properties, such as the free energies of different states of a system, which in turn requires well-converged sampling of the ensemble of possible structures. Enhanced sampling techniques are often applied to provide faster convergence than is possible with traditional molecular dynamics simulations. Hamiltonian replica exchange molecular dynamics (H-REMD) is a particularly attractive method, as it allows the incorporation of a variety of enhanced sampling techniques through modifications to the various Hamiltonians. In this work, we study the enhanced sampling of the RNA tetranucleotide r(GACC) provided by H-REMD combined with accelerated molecular dynamics (aMD), where a boosting potential is applied to torsions, and compare this to the enhanced sampling provided by H-REMD in which torsion potential barrier heights are scaled down to lower force constants. We show that H-REMD and multidimensional REMD (M-REMD) combined with aMD does indeed enhance sampling for r(GACC), and that the addition of thetemperature dimension in the M-REMD simulations is necessary to efficientlysample rare conformations. Interestingly, we find that the rate ofconvergence can be improved in a single H-REMD dimension by simplyincreasing the number of replicas from 8 to 24 without increasingthe maximum level of bias. The results also indicate that factorsbeyond replica spacing, such as round trip times and time spent ateach replica, must be considered in order to achieve optimal samplingefficiency.