Microcalorimetry of heat capacity and volumetric changes in biomolecular interactions—the link to solvation?

Abstract

Changes in solvation play a central role in the thermodynamics of non-covalent interactions in solution, especially in water, yet there are relatively few techniques available to probe this unambiguously. Experimental studies of the thermodynamics of biomolecular interactions in water have exposed two significant empirical observations. The first, well known from the very earliest applications of microcalorimetry, is that processes such as protein folding, ligand binding, and protein–protein association almost always occur with a decrease in overall heat capacity of the system (negative ΔC p). This results in a strong temperature dependence of the enthalpy of interaction that has, historically, been usually attributed to solvation changes, though more generally it has been shown to be an inevitable consequence of processes involving the cooperative interaction of multiple weak interactions. More recently using pressure perturbation calorimetry (PPC), we have shown that such interactions in the same systems also occur with significant decreases in molar thermal expansibility (negative ΔE°) that can be related to the loss of solvation during complexation. The apparently strong correlation between ΔC p and ΔE° potentially leads to a generic picture of the thermodynamics of macromolecular interactions in water in which both solvation and conformational fluctuation play a much more prominent role than has been hitherto supposed.