Figure 2.

Free energy of solvating water molecules varies as a function of position on a given solvent-accessible surface. Solute surfaces are imprinted in (“written to”) their solvating water in the form of H-bond propensity patterns, analogous to a three-dimensional bitmap (H-bond depleted and enriched solvating water molecules are denoted by a lightning bolt and heart, respectively), resulting in highly nonisotropic solvation free energy fields. Solvation free energy fields are “read” by state transition-induced unfavorable water transfers to/from bulk solvent and solvation (such that the overall state transition barrier equates to the total cost of such transfers). Polar/charged surfaces promote H-bond enriched solvation relative to bulk solvent, resulting in decreased solvation free energy (the expulsion of which incurs a free energy cost). Nonpolar surfaces promote H-bond depleted solvation relative to bulk solvent, resulting in increased solvation free energy (the expulsion of which results in a free energy gain).