Common Folding Mechanism of a Peptide Revealed by Multiple MD Simulations

Abstract

Here, we report on the folding of a 15 residue beta-hairpin peptide (Peptide 1) using multiple unbiased, atomistic molecular dynamics (MD) simulations. Fifteen independent MD trajectories, each 2.5 microseconds-long for a total of 37.5 microseconds are performed in explicit solvent, at room temperature and without the use of enhanced sampling techniques. The computed folding time of 1-1.5 microseconds obtained from the simulations is in good agreement with experiment. A common folding mechanism is observed, in which the turn is always found to be the major determinant in initiating the folding process, followed by cooperative formation of the inter-strand hydrogen bonds and the side chain packing. Furthermore, direct transition to the folded state from fully unstructured conformations does not take place. Instead, the native hairpin is always observed to form from partially structured conformations involving a non-native (ESYI) turn from which the native (NPDG) turn forms, triggering the folding to the beta-hairpin.