Replica exchange molecular dynamic simulations for the conformational analyses of synthetic peptides

Different combinations of forcefield and implicit solvation models were compared against their ability to predict the native conformation of a selection of helical peptides, β-hairpins and intrinsically disordered peptides (IDP), using Replica Exchange Molecular Dynamics (REMD) simulations.[1] A unique combination of force field and implicit solvent model able to accurately predict the experimental structure of all the considered systems was not found. However, we observed that that the force fields of the ff99SB series coupled with GB-Neck2 reasonably discriminated helices from IDPs. Conversely, a decent prediction of β-hairpin conformations was achieved by combining the ff96 forcefield with either GC-OBC(II) or GB-Neck2 solvent models. Consequently, in order to achieve a true prediction of an unknown peptide, a set of two different simulations are suggested: the first using any of the ff99SB/ildn/ildn-φ force fields coupled to GB-Neck2, the second using the ff96 force field coupled to GB-Neck2 or GB-OBC(II). Using this knowhow, we applied REMD simulations to predict the conformation of different bioactive or potentially bioactive peptides containing non-natural amino acids. In particular, we will discuss examples concerning helical peptides,[2] cyclopeptides,[3] β-hairpins,[4] and γ-turns.[5]