MOLECULAR MECHANICS ANALYSIS OF PEPTIDE GROUP HYDROGEN-BONDING COOPERATIVITY AND INFLUENCE ON PHI AND PSI ROTATIONAL BARRIERS

Molecular mechanics calculations are performed on N-methylacetamide (N MA) hydrogen bonded with water molecules and the results are compared with those from high-level ab initio quantum chemical calculations (H. Guo and M. Karplus, J. Phys. Chem., 96 (1992) 7273). The ab initio re sults suggest that water molecules bind cooperatively to the peptide g roup of NMA; this effect is mostly reproduced by the empirical force f ield. The influence of water molecule hydrogen bonding on the barriers to rotation around the N-C(alpha) and C(alpha)-C' bonds in NMA is als o investigated. To reproduce the ab initio results for the C(alpha)-C' (PSI) rotational barrier, it is necessary to modify the form of the p otential function such that the intrinsic force constant for PSI rotat ion varies with the hydrogen bonding state of the peptide group. For t he N-C(alpha) (PHI) rotation the molecular mechanics barrier contains a large contribution from intermolecular van der Waals effects in the hydrogen bonded complexes.