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 st udy hydrogen bond interactions in dimers of N-methylacetamide (NMA), in NMA -water complexes, and in human lysozyme. The potential energy surface is fo und to be determined by the interactions of entire peptide groups (O=Ci-1-N -i-H) or water molecules rather than by single donor and acceptor groups. T he 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 par ameters that describe the hydrogen bond. Potential energy surfaces were als o examined in the presence and absence of explicit solvent molecules. The r esults suggest that both competing hydrogen bond interactions and the therm al motion of atoms broaden the distribution of low energy donor-acceptor co ntacts. Comparisons are made with a statistical analysis of mainchain hydro gen bond donor and acceptor contacts in high-resolution crystal structures of nonhomologous proteins. Interaction energies and geometries of the NMA m odel system mimic those found in folded polypeptide chains. All systems are characterized by a minimum in the population of donor-acceptor contacts at interaction distances of 2.4-2.6 Angstrom. This minimum originates from sp atial constraints that are enhanced by electrostatic interactions in enviro nments that are characterized by competition for hydrogen bonding interacti ons. The presence of such a minimum in the distribution of donor-acceptor c ontacts supports the definition of hydrogen bonds by geometrical cutoff cri teria with a donor-hydrogen acceptor distance of less than 2.5 Angstrom and an angle of deviation not more than 90 degrees from linearity of the donor , donor-hydrogen and acceptor atoms.