Influences of lone-pair electrons on directionality of hydrogen bonds formed by hydrophilic amino acid side chains in molecular dynamics simulation

The influence of lone-pair electrons on the directionality of hydrogen bonds that are formed by oxygen and nitrogen atoms in the side chains of nine hydrophilic was investigated using molecular dynamics simulations. The simulations were conducted using two types of force fields; one incorporated lone-pair electrons placed at off-atom sites and the other did not. The density distributions of the hydration water molecules around the oxygen and nitrogen atoms were calculated from the simulation trajectories, and were compared with the empirical hydration distribution functions, which were constructed from a large number of hydration water molecules found in the crystal structures of proteins. Only simulations using the force field explicitly incorporating lone-pair electrons reproduced the directionality of hydrogen bonds that is observed in the empirical distribution functions for the deprotonated oxygen and nitrogen atoms in the sp ²-hybridization. The amino acids that include such atoms are functionally important glutamate, aspartate, and histidine. Therefore, a set of force field that incorporates lone-pair electrons as off-atom charge sites would be effective for considering hydrogen bond formation by these amino acids in molecular dynamics simulation studies.