Hydrogen Bond Energetics: A Simulation and Statistical Analysis of N-Methyl Acetamide (NMA), Water, and Human Lysozyme†

Energy minimization and molecular dynamics simulations have been used to study hydrogen bond interactions in dimers of N-methylacetamide (NMA), in NMA−water complexes, and in human lysozyme. The potential energy surface is found to be determined by the interactions of entire peptide groups (OCi-1−Ni−H) or water molecules rather than by single donor and acceptor groups. The contact distance between the donor hydrogen and the acceptor as well as the angle of the bond at the donor hydrogen are the principal geometric parameters that describe the hydrogen bond. Potential energy surfaces were also examined in the presence and absence of explicit solvent molecules. The results suggest that both competing hydrogen bond interactions and the thermal motion of atoms broaden the distribution of low energy donor−acceptor contacts. Comparisons are made with a statistical analysis of mainchain hydrogen bond donor and acceptor contacts in high-resolution crystal structures of nonhomologous proteins. Interaction energies...