Free energy and structure of polyproline peptides: An ab initio and classical molecular dynamics investigation

Abstract

AbstractDepending on their environment, polyproline peptides form chiral helices that may be either left‐ (PPII) or right‐handed (PPI). Here, we have characterized both the structure and free energy landscapes of Ace‐(Pro)n‐Nme (n an integer less than 13) peptides, in vacuo and in implicit water environments. Both ab initio and classical molecular dynamics methods were used. In terms of the latter, we used a recently developed Adaptively Biased Molecular Dynamics (ABMD) method in conjunction with three different force fields (ff99, ff99SB, ff03) and two different Generalized Born models for the implicit solvent environment. Specifically, the ABMD method provides for an accurate description of the free energy landscapes in terms of a set of collective variables, which were carefully chosen as to reflect the “slow modes” of the polyproline peptides. These are primarily based on the cis‐trans isomerization associated with the prolyl bonds. In agreement with recent experimental results, the peptides form not only the pure PPII or PPI structures but also a large number of stable conformers having more or less similar free energies, whose distributions we have characterized. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010