Background: The partial specific volume of a protein is an experimental quantity containing information about solute-solvent interactions and protein hydration. We use a hydration-shell model to partition the partial specific volume into an intrinsic volume occupied by the protein and a change in the volume occupied by the solvent resulting from the solvent interactions with the protein. We seek to extract microscopic information about protein hydration and unfolding from experimental volume measurements without using computer simulations. We employ the idea that the protein-solvent interaction will be proportional to the surface area of the protein.
Results: A linear relationship is obtained when the difference between the experimental protein partial specific volume and its intrinsic volume is plotted as a function of the protein solvent-accessible surface area. The effect of using different protein volume definitions on the analysis of protein volumetric properties is discussed. Volumetric data are used to test a model for the unfolded state of proteins and to make predictions about the denatured state.
Conclusions: The linear relationship between hydration-shell volume change and accessible surface area reflects the similar surface properties (fractional composition of nonpolar, polar and charged surface) among a diverse set of proteins. This linear relationship is found to be independent of how the solution is partitioned into solute and solvent components. The interpretation of hydration shell versus bulk water properties is found to be very model dependent, however. The maximally exposed unfolded protein model is found to be inconsistent with experimental volume changes of unfolding.