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

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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 Δ) that can be related to the loss of solvation during complexation. The apparently strong correlation between ΔC p and Δ 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.

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References

  1. Cooper A. Thermodynamic analysis of biomolecular interactions. Curr Opin Chem Biol. 1999;3(5):557–63.

    Article  CAS  Google Scholar 

  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.

  3. Plotnikov VV, Brandts JM, Lin L-N, Brandts JF. A new ultrasensitive scanning calorimeter. Anal Biochem. 1997;250(2):237–44.

    Article  CAS  Google Scholar 

  4. Wiseman T, Williston S, Brandts JF, Lin LN. Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal Biochem. 1989;179(1):131–7.

    Article  CAS  Google Scholar 

  5. Lin LN, Brandts JF, Brandts JM, Plotnikov V. Determination of the volumetric properties of proteins and other solutes using pressure perturbation calorimetry. Anal Biochem. 2002;302(1):144–60.

    Article  CAS  Google Scholar 

  6. Jung HI, Cooper A, Perham RN. Identification of key amino acid residues in the assembly of enzymes into the pyruvate dehydrogenase complex of Bacillus stearothermophilus: a kinetic and thermodynamic analysis. Biochemistry. 2002;41(33):10446–53.

    Article  CAS  Google Scholar 

  7. Jung HI, Cooper A, Perham RN. Interactions of the peripheral subunit-binding domain of the dihydrolipoyl acetyltransferase component in the assembly of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Eur J Biochem. 2003;270(22):4488–96.

    Article  CAS  Google Scholar 

  8. Jung H-I, Bowden SJ, Cooper A, Perham RN. Thermodynamic analysis of the binding of component enzymes in the assembly of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Protein Sci. 2002;11(5):1091–100.

    Article  CAS  Google Scholar 

  9. Cooper A. Heat capacity effects in protein folding and ligand binding: a re-evaluation of the role of water in biomolecular thermodynamics. Biophys Chem. 2005;115(2–3):89–97.

    Article  CAS  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.

    Article  CAS  Google Scholar 

  11. Clarke C, Woods RJ, Gluska J, Cooper A, Nutley MA, Boons GJ. Involvement of water in carbohydrate-protein binding. J Am Chem Soc. 2001;123(49):12238–47.

    Article  CAS  Google Scholar 

  12. Cooper A. Protein heat capacity: an anomaly that maybe never was. J Phys Chem Lett. 2010;1(22):3298–304.

    Article  CAS  Google Scholar 

  13. Cameron D, Cooper A. Pressure perturbation calorimetry of solvation changes in cyclodextrin complexes. J Incl Phenom Macrocycl Chem. 2002;44(1–4):279–82.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

  15. Cooper A, Cameron D, Jakus J, Pettigrew GW. Pressure perturbation calorimetry, heat capacity and the role of water in protein stability and interactions. Biochem Soc Trans. 2007;35:1547–50.

    Article  CAS  Google Scholar 

  16. Mitra L, Smolin N, Ravindra R, Royer C, Winter R. Pressure perturbation calorimetric studies of the solvation properties and the thermal unfolding of proteins in solution—Experiments and theoretical interpretation. Phys Chem Chem Phys. 2006;8(11):1249–65.

    Article  CAS  Google 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.

    CAS  Google Scholar 

  18. Batchelor JD, Olteanu A, Tripathy A, Pielak GJ. Impact of protein denaturants and stabilizers on water structure. J Am Chem Soc. 2004;126(7):1958–61.

    Article  CAS  Google Scholar 

  19. Dragan AI, Russell DJ, Privalov PL. DNA hydration studied by pressure perturbation scanning microcalorimetry. Biopolymers. 2009;91(1):95–101.

    Article  CAS  Google Scholar 

  20. Heerklotz H, Seelig J. Application of pressure perturbation calorimetry to lipid bilayers. Biophys J. 2002;82(3):1445–52.

    Article  CAS  Google Scholar 

  21. Mitra L, Oleinikova A, Winter R. Intrinsic volumetric properties of trialanine isomers in aqueous solution. ChemPhysChem. 2008;9(18):2779–84.

    Article  CAS  Google Scholar 

  22. Mitra L, Rouget JB, Garcia-Moreno B, Royer CA, Winter R. Towards a quantitative understanding of protein hydration and volumetric properties. ChemPhysChem. 2008;9(18):2715–21.

    Article  CAS  Google Scholar 

  23. Rayan G, Tsamaloukas AD, Macgregor RB, Heerklotz H. Helix-coil transition of DNA monitored by pressure perturbation calorimetry. J Phys Chem B. 2009;113(6):1738–42.

    Article  CAS  Google Scholar 

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Acknowledgements

The Biological Microcalorimetry Facility in Glasgow was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC).

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Correspondence to Alan Cooper.

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Cooper, A. Microcalorimetry of heat capacity and volumetric changes in biomolecular interactions—the link to solvation?. J Therm Anal Calorim 104, 69–73 (2011). https://doi.org/10.1007/s10973-011-1285-3

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