Computational assesment of the entropy of solvation of small-sized hydrophobic entities

TL;DR

This study uses molecular dynamics simulations with a polarizable force field to analyze how the entropy of hydrophobic solvation of small molecules varies with temperature, supporting the Lum Chandler Weeks theory.

Contribution

It extends temperature-dependent free energy calculations of hydrophobic hydration using a polarizable water model across a wide temperature range.

Findings

Entropy of small hydrophobic cavities is negative across temperatures.

Polarizable force field accurately models water properties over temperature range.

Results support the Lum Chandler Weeks theory on hydrophobic hydration.

Abstract

A high level polarizable force field is used to study the temperature dependence of hydrophobic hydration of small-sized molecules from computer simulations. Molecular dynamics (MD) simulations of liquid water at various temperatures form the basis of free energy perturbation calculations that consider the onset and growth of a repulsive sphere. This repulsive sphere acts as a model construct for the hydrophobic species. In the present study, an extension is pursued for seven independent target temperatures, ranging from close to the freezing point almost up to the boiling point of liquid water under standard conditions. Care is taken to maintain proper physico-chemical model descriptions by cross-checking with experimental water densities at the selected target temperatures. The polarizable force field description of molecular water turns out to be suitable throughout the entire temperature domain considered. Derivatives of the computed free energies of hydrophobic hydration with respect to the temperature give access to the changes in entropy. In practice the entropy differential is determined from the negative of the slope of tangential lines formed at a certain target temperature in the free energy profile. The obtained changes in entropy are negative for small-sized cavities, and hence reconfirm the basic ideas of the Lum Chandler Weeks theory on hydrophobic hydration of small-sized solutes.