Molecular dynamics simulations of polypeptide conformations in water: A comparison of alpha, beta, and poly(Pro)II conformations

A significant fraction of the so-called "random coil" residues in globular proteins exists in the left-handed poly(Pro)II conformation. In order to co mpare the behavior of this secondary structure with that of the other regul ar secondary structures, molecular dynamics simulations, with the GROMOS su ite of programs, of an alanine octapeptide in water, in alpha-helix, beta-s trand, and left-handed poly(Pro)II conformations, have been performed. Our results indicate a limited flexibility for the alpha-helix conformation and a relatively larger flexibility for the beta-strand and poly(Pro)II confor mations. The behavior of oligopeptides with a starting configuration of bet a-strand and poly(Pro)II conformations, both lacking interchain hydrogen bo nds, were similar. The (phi, psi) angles reflect a continuum of structures including both beta and P-II conformations, but with a preference for local P-II regions. Differences in the network of water molecules involved in hy drogen bonding with the backbone of the polypeptide were observed in local regions of beta and P-II conformations. Such water bridges help stabilize t he P-II conformation relative to the beta conformation. Proteins 1999;36:40 0-406, (C) 1999 Wiley-Liss, Inc.