Quantifying water hydrogen bonding from the surface electrostatic potential at varying iso-density contours

Abstract

The electrostatic potential plotted on varying contours (VS) of the electron density guides us in the understanding of how water interactions exactly take place. Water—H2O—is extremely well balanced, having a hydrogen VS,max and an oxygen VS,min of similar magnitude. As such, it has the capacity to donate and accept hydrogen bonds equally well. This has implications for the interactions that water molecules form, which are reviewed here, first in water–small molecule models and then in complex sites as lactose and its crystals and in protein–protein interfaces. Favorable and unfavorable interactions are evaluated from the electrostatic potential plotted on varying contours of the electronic density, allowing these interactions to be readily visualized. As such, with one calculation, all interactions can be analyzed by gradually looking deeper into the electron density envelope and finding the nearly touching contour. Its relation with interaction strength has the electrostatic potential to be used in scoring functions. When properly implemented, we expect this approach to be valuable in modeling and structure validation, avoiding tedious interaction strength calculations. Here, applied to water interactions in a variety of systems, we conclude that all water interactions take the same general form, with water behaving as a “neutral” agent, allowing its interaction partner to determine if it donates or accepts a hydrogen bond, or both, as determined by the highest possible interaction strength(s).