Conformational study on trans- and cis-N-acetyl-N'-methylamides of Pro-Xaa dipeptides

Conformational free energy calculations using an empirical potential (ECEPP/2) and the hydration shell model were carried out on the N-acetyl-N'-methylamides of Pro-Xaa dipeptides (Xaa = Ala, Leu, Val, Gly, Cys, Met, Phe, Tyr, Asn, Asp, and Ser) with trans and cis peptide bonds preceding proline residue in the unhydrated and hydrated states. As compared with the results obtained by using the earlier version of ECEPP, the values of beta-bend probabilities are doubled. The average calculated population of cis-dipeptide is about 4%, which is close to the abundance obtained from the analysis of X-ray crystal structures of proteins. The beta-bends are the most dominant structures of cis-dipeptides. Type I, usually having intramolecular hydrogen bonds, contributes greatly to the beta-bend conformations of trans- and cis-dipeptides. However, type I beta-bends of cis-dipeptides do not have any hydrogen bonds. By including the hydration, the beta-bend probabilities for trans- and cis-dipeptides decreased, indicating that the interactions of water molecules with a backbone or side-chain may force the dipeptides to be more distorted or extended. In particular, type II is found to be a dominant beta-bend conformation of trans- and cis-Pro-Gly dipeptides in both the unhydrated and hydrated states. In general, the calculated propensities for Pro-Xaa dipeptides to adopt beta-bend conformations are reasonably consistent with available experimental data. From comparing conformations of Pro and Xaa residues in the dipeptides and single residues, we found that inter-residue interactions and hydration are of importance in determining the conformational properties of the Pro-Xaa dipeptide.