On empirical decomposition of volumetric data.

Abstract

Volumetric characterization of proteins and their recognition events has been instrumental in providing information on the role of intra- and intermolecular interactions, including hydration, in stabilizing biomolecules. The credibility of molecular models and interpretation schemes used to rationalize experimental data are essential for the validity of microscopic insights derived from volumetric results. Current empirical schemes used to interpret volumetric data suffer from a lack of theoretical and computational substantiation. In this contribution, we take advantage age of recent MD simulations of proteins in solution coupled with Voronoi-Delaunay tessellation of simulated structures that have provided an exceptional level of structural detail on the nature of protein-water interfaces. We use these structural insights to re-evaluate empirical frameworks used for interpretation of volumetric data. An important issue in this respect is the actual dividing surface between water and protein atoms that is used in volumetric studies when the solute and solvent are treated as hard spheres enclosed within their respective van der Waals surfaces. In one development, using Voronoi tessellation of MD simulated protein-water systems the dividing surface has been defined as the points equidistant from the water and protein atoms. The interstitial void volume between the solute and the dividing surface corresponds to thermal volume envisaged by Scaled Particle Theory. In this communication, we explicitly account for the contributions of thermal volume to the partial molar volume, compressibility, and expansibility of proteins and re-examine and redefine the intrinsic and hydration volumetric contributions. We discuss the implications of our results for protein transitions and association events.