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 (NMA) 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 results suggest that water molecules bind cooperatively to the peptide group of NMA; this effect is mostly reproduced by the empirical force field. 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 also investigated. To reproduce the ab initio results for the C(alpha)-C' (PSI) rotational barrier, it is necessary to modify the form of the potential function such that the intrinsic force constant for PSI rotation varies with the hydrogen bonding state of the peptide group. For the N-C(alpha) (PHI) rotation the molecular mechanics barrier contains a large contribution from intermolecular van der Waals effects in the hydrogen bonded complexes.