Comparisons of potential energy landscapes and conformations of polyalanine with different force fields by new molecular dynamics simulation protocols

COMP 216

Zunnan Huang, znhuang@chemdept.chem.ou.edu and Ralph A. Wheeler, rawheeler@chemdept.chem.ou.edu. Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Rm. 208, Norman, OK 73019
Molecular simulations have been applied extensively for studying protein structure and dynamics. However, conventional molecular dynamics (MD) simulations have extreme difficulty sampling phase space sufficiently to predict the naturally folded structures of proteins. Here we report newly developed MD protocols called trajectory and energy perturbed replica microcanonical ensemble search simulations, which can explore the potential energy surfaces of proteins and efficiently sample myriad potential energy minima representing diverse conformations. We performed the new MD simulation to investigate the global and local potential energy minima of a short polyalanine peptide (13 residues) in vacuo. Two commonly used AMBER MD force fields for protein systems were tested. Comparisons of the secondary structural conformations and energy minima of this polypeptide highlight likely differences in potential energy landscapes built on different force fields. The results imply that although beta-sheets have minima located at higher potential energies than alpha-helices for both force fields, the significantly different distribution of internal energies of beta-sheets relative to helices accounts for the observation that helical conformations are favored for AMBER 99, whereas AMBER96 shows more extensive phase space sampling of both helical and beta-sheet conformations.