Volumetric analysis of the energetics of protein hydration

Abstract

Water plays a dominant role in all biomacromolecular folding and binding events. For decades, volumetric observables have been used to characterize the hydration properties of solutes. These studies aimed at gaining insights into the number of water molecules solvating solutes or changes in these numbers upon folding and binding events involving biopolymers. However, the link between the volumetric properties of solutes and the energetics of their hydration has been missing. This deficiency limits the potential benefits of the use of volumetric measurements in hydration studies. In this contribution, we derive a possible link between the free energy of hydration of amino acid side chains and a select set of other organic compounds and their volumetric characteristics. Potentially, this approach can be used to estimate the contribution of hydration to the energetics of protein folding and binding reactions.