Dissecting the energetics of hydrophobic hydration of polypeptides.

The energetics of water proximal to apolar groups is analyzed from a statistical perspective in the realistic context of polypeptide hydration. Analysis of a series of molecular dynamics simulations of a 16-residue polypeptide in water reveals a correlation between hydrogen bond energy and local packing when there is overcoordination of the water molecules around hydrogen bonds. We show that the origin of the greater strength of hydrogen bonds in the hydrophobic hydration shell when compared to bulk water correlates with the depletion of water nearest neighbors around apolar moieties. The water molecules in the hydrophobic hydration shell sample the hydrogen bonding patterns present in comparable relatively low coordination regions of bulk water. We also find that for hydrophobic hydration shell water molecules the probability distribution of hydrogen bond energies is independent of the number of hydrogen bonds formed with other water molecules inside and outside the polypeptide hydration shell. This lack of correlation of hydrogen bond energy with hydrogen bond number leads to a remarkably accurate simplified statistical model for the energetics of hydrophobic hydration.