How large are the volume changes accompanying protein transitions and binding?

We present a simple model to describe volume changes accompanying protein folding and binding events. The model enables one to resolve the changes in volume accompanying conformational transitions of proteins as well as association of proteins with other molecules in terms of the intrinsic, thermal and interaction (hydration) contributions. The thermal contribution to protein volume results from thermally activated mutual vibrational motions of contacting solute and solvent molecules. Our calculations suggest that near zero volume changes accompanying protein folding and binding events reflect compensation between significant changes in the intrinsic, thermal and interaction terms. We have quantitatively estimated these terms as a function of the protein's molecular weight and degree of its unfolding. Results described in this work lay foundation for more reliable and physically justified interpretations of volumetric data on protein folding and binding events. We also discuss potential ways of extending applications of our model to analyzing other macromolecular systems and events, including drug-DNA and protein-DNA interactions and helix-to-helix and helix-to-coil transitions of nucleic acids.