The Thermodynamics of Folding of a β Hairpin Peptide Probed Through Replica Exchange Molecular Dynamics Simulations

Abstract

Peptides that possess a well defined native state are ideal model systems to study the folding of proteins. They possess many of the complexities of larger proteins, yet their small size renders their study computationally tractable. Recent advances in sampling techniques, including replica exchange molecular dynamics, now permit a full characterization of the thermodynamics of folding of small peptides. These simulations not only yield insight into the folding of larger proteins, but equally importantly, they allow, through comparison with experiment, an objective test of the accuracy of force fields, water models and of different numerical schemes for dealing with electrostatic interactions. In this account, we present a molecular dynamics simulation of a small β-hairpin peptide using the replica exchange algorithm and illustrate how this enhanced sampling scheme enables a thorough characterization of the native and unfolded states, and sheds new light into its folding mechanism.