Replica-Exchange Accelerated Molecular Dynamics (REXAMD) Applied to Thermodynamic Integration

Abstract

Accelerated molecular dynamics (AMD) is an efficient strategy for accelerating the sampling of molecular dynamics simulations, and observable quantities such as free energies derived on the biased AMD potential can be reweighted to yield results consistent with the original, unmodified potential. In conventional AMD the reweighting procedure has an inherent statistical problem in systems with large acceleration, where the points with the largest biases will dominate the reweighted result and reduce the effective number of data points. We propose a replica exchange of various degrees of acceleration (REXAMD) to retain good statistics while achieving enhanced sampling. The REXAMD method is validated and benchmarked on two simple gas-phase model systems, and two different strategies for computing reweighted averages over a simulation are compared.

Current state of theoretical and experimental studies of the voltage-dependent anion channel (VDAC)

“…It builds on the previous work in tempered-simulation applications to sampling enhancements [103–106]. Similar to traditional T-REMD [105, 107] where running replicas at different temperatures provides substantial acceleration in sampling, the rate at which the sampling of reaction path can be considerably enhanced by coordinate swapping between independent simulations generated for different Hamiltonians generated by Umbrella-Sampling, Thermodynamic Integration of Free Energy Perturbation simulations [21, 101, 107–111]. For PMF calculation with US, considering N copies of a system that are identical except for some differences in a small number of parameters, it is possible to make ordered lists of these systems such that the difference in the parameters is smallest for the nearest neighbours in the list.…”

Enhanced Sampling in Molecular Dynamics Using Metadynamics, Replica-Exchange, and Temperature-Acceleration

“…Several recipes for choosing the modified Hamiltonian have been proposed in the literature [207][208][209][210][211][212][213][214][215][216][217][218][219]. Among these, a notable idea is that of solute tempering [208,217] which is used for the simulation of solvated biomolecules.…”

Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials

“…In contrast, V nonbonded ( r ) only includes the nonbonded (L-J and Coulomb) interactions within the cutoff distance of the selected atoms. Moreover once we select the rotatable bonds and related atoms for flattening, the functions of V bonded ( r ) and V nonbonded ( r ) are fixed using the corresponding force field parameters and we do not need to decide what values are suitable unlike other accelerated methods using rescaling interactions 36,37,48 or adding biasing potentials 33,34,49–51 . The magnitude ( λ f ) of the biasing potentials can be expressed as a parametric function of λ b simply as follows, $${\lambda }_f=\{\begin{array}{cc}2{\lambda }_b& \text{ if }{\lambda }_b\le 0.5\\ 2-2{\lambda }_b& {\lambda }_b>0.5\end{array}$$ Using this simple function, the biasing potentials are automatically turned off ( λ f = 0 ) at both the fully coupled ( λ b = 1) and decoupled ( λ b = 0) physical states.…”

“…33,34,49–51 The REST2 method lowers the energy barriers (equivalent to increasing the temperature) of hotspot regions (side-chains of receptors and/or mutated functional groups of ligands in a protein-ligand binding site) by rescaling the inter or intra-molecular interactions using preselected parameters, and enhances the conformational sampling in free energy perturbation (FEP) calculations for relative binding free energies. In these HREMD methods the rescaling parameters or the functions of biasing potentials need to be preselected carefully by estimating the heights of energy barriers varied for different systems.…”