Prediction of helical peptide folding in an implicit water by a new molecular dynamics scheme with generalized effective potential

Previously we demonstrated the effectiveness of the recently developed q-jumping molecular dynamics simulation method (q-jumping MD) in vacuo for fast conformational searches and optimization purposes. In this work we attempt to further investigate the conformational searching capability of this new scheme by applying it to folding problems of helical peptides containing fully charged side chains in an implicit water. With a slightly modified q-jumping MD method using the all-atom empirical force field and its generalized Born solvation model, the current simulations at T=300 K all lead to fast helix folding with broad potential energy fluctuations, starting from their extended (linear) conformations. The present study demonstrates that this new MD scheme greatly enhances the rate of conformational changes, making it possible to explore low energy conformations of peptides in aqueous environments in a reasonably short time. Therefore, the all-atom based theoretical prediction of native solution structures of more challenging systems, such as helix bundles, beta-sheets, and even small proteins may be a realistic possibility. (C) 2002 American Institute of Physics.