Water Density Fluctuations Relevant to Hydrophobic Hydration are Unaltered by Attractions

TL;DR

This study shows that water density fluctuations relevant to hydrophobic hydration remain unchanged by attractive interactions when confined to the hydration shell, aiding more efficient hydration free energy calculations.

Contribution

It demonstrates that attractive solute-water interactions in the hydration shell do not significantly affect core water density fluctuations, extending understanding to realistic hydrophobic solutes.

Findings

Attractive fields in the hydration shell do not alter core water fluctuations.

Linear response theory accurately predicts free energetics of attraction.

Strategies for efficient hydration free energy estimation are proposed.

Abstract

An understanding of density fluctuations in bulk water has made significant contributions to our understanding of the hydration and interactions of idealized, purely repulsive hydrophobic solutes. To similarly inform the hydration of realistic hydrophobic solutes that have dispersive interactions with water, here we characterize water density fluctuations in the presence of attractive fields that correspond to solute-water attractions. We find that when the attractive field acts only in the solute hydration shell, but not in the solute core, it does not significantly alter water density fluctuations in the solute core region. We further find that for a wide range of solute sizes and attraction strengths, the free energetics of turning on the attractive fields in bulk water are accurately captured by linear response theory. Our results also suggest strategies for more efficiently estimating hydration free energies of realistic solutes in bulk water and at interfaces.