Peptide Folding Kinetics from Replica Exchange Molecular Dynamics

TL;DR

This paper demonstrates how to extract accurate protein folding and unfolding rates from replica-exchange molecular dynamics simulations by analyzing trajectory segments and constructing a master equation, achieving results consistent with long equilibrium simulations.

Contribution

It introduces a method to derive kinetic rates from REMD simulations using short trajectory segments and a master equation approach, providing a new way to study protein kinetics.

Findings

Accurate folding/unfolding rates can be obtained from REMD with 5 ps exchange times.

Rates in the range of 1/(100 ns) to 1/(1 ns) are consistent with long MD results.

The method is validated on a helical peptide in explicit water.

Abstract

We show how accurate kinetic information, such as the rates of protein folding and unfolding, can be extracted from replica-exchange molecular dynamics (REMD) simulations. From the brief and continuous trajectory segments between replica exchanges, we estimate short-time propagators in conformation space and use them to construct a master equation. For a helical peptide in explicit water, we determine the rates of transitions both locally between microscopic conformational states and globally for folding and unfolding. We show that accurate rates in the ~1/(100 ns) to ~1/(1 ns) range can be obtained from REMD with exchange times of 5 ps, in excellent agreement with results from long equilibrium molecular dynamics.