Peptide folding kinetics from replica exchange molecular dynamics.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Bethesda, Maryland 20892-0520, USA.

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 approximately 1(100 ns) to approximately 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.

PMID: 18517321 [PubMed - indexed for MEDLINE]