Combining Enhanced Sampling with Experiment Directed Simulation of the GYG peptide

TL;DR

This paper integrates enhanced sampling techniques with experiment directed simulation to improve the accuracy and sampling efficiency of molecular dynamics simulations of the GYG peptide, guided by NMR data.

Contribution

It introduces a novel combination of experiment directed simulation with parallel-tempering methods to enhance sampling in biological molecular simulations.

Findings

Enhanced sampling achieved with parallel-tempering methods.

Accurate matching of experimental NMR data.

Demonstrated on GYG peptide in explicit water.

Abstract

Experiment directed simulation is a technique to minimally bias molecular dynamics simulations to match experimentally observed results. The method improves accuracy but does not address the sampling problem of molecular dynamics simulations of large systems. This work combines experiment directed simulation with both the parallel-tempering and parallel-tempering well-tempered ensemble replica-exchange methods to enhance sampling of experiment directed simulations. These methods are demonstrated on the GYG tripeptide in explicit water. The collective variables biased by experiment directed simulation are chemical shifts, where the set-points are determined by NMR experiments. The results show that it is possible to enhance sampling with either parallel-tempering and parallel-tempering well-tempered ensemble in the experiment directed simulation method. This combination of methods provides a novel approach for both accurately and exhaustively simulating biological systems.