Microcalorimetry of heat capacity and volumetric changes in biomolecular interactions—the link to solvation?
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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 ΔCp). 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 ΔCp 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.
KeywordsProtein folding Ligand binding Thermodynamics Fluctuations
The Biological Microcalorimetry Facility in Glasgow was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC).
- 2.Guerlac H. Joseph Black’s work on heat. In: Simpson ADC, editor. Joseph Black 1728–1799: a commemorative symposium. Edinburgh: Royal Scottish Museum; 1982.Google Scholar
- 10.Cooper A, Johnson CM, Lakey JH, Nollmann M. Heat does not come in different colours: entropy-enthalpy compensation, free energy windows, quantum confinement, pressure perturbation calorimetry, solvation and the multiple causes of heat capacity effects in biomolecular interactions. Biophys Chem. 2001;93(2–3):215–30.CrossRefGoogle Scholar
- 14.Cameron DL, Jakus J, Pauleta SR, Pettigrew GW, Cooper A. Pressure perturbation calorimetry and the thermodynamics of noncovalent interactions in water: comparison of protein–protein, protein–ligand, and cyclodextrin–adamantane complexes. J Phys Chem B. 2010;114:16228–35. doi:10.1021/jp107110t.CrossRefGoogle Scholar
- 17.Okoro L, Winter R. Pressure perturbation calorimetric studies on phospholipid-sterol mixtures. Zeitschrift Fur Naturforschung Section B (a Journal of Chemical Sciences). 2008;63(6):769–78.Google Scholar