Pressure perturbation calorimetry, heat capacity and the role of water in protein stability and interactions.
It is widely acknowledged, and usually self-evident, that solvent water plays a crucial role in the overall thermodynamics of protein stabilization and biomolecular interactions. Yet we lack experimental techniques that can probe unambiguously the nature of protein-water or ligand-water interactions and how they might change during protein folding or ligand binding. PPC (pressure perturbation calorimetry) is a relatively new technique based on detection of the heat effects arising from application of relatively small pressure perturbations (+/-5 atm; 1 atm=101.325 kPa) to dilute aqueous solutions of proteins or other biomolecules. We show here how this can be related to changes in solvation/hydration during protein-protein and protein-ligand interactions. Measurements of 'anomalous' heat capacity effects in a wide variety of biomolecular interactions can also be related to solvation effects as part of a quite fundamental principle that is emerging, showing how the apparently unusual thermodynamics of interactions in water can be rationalized as an inevitable consequence of processes involving the co-operative interaction of multiple weak interactions. This leads to a generic picture of the thermodynamics of protein folding stabilization in which hydrogen-bonding plays a much more prominent role than has been hitherto supposed.
Cooper
A
A
WestChem Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K. alanc@chem.gla.ac.uk
Cameron
D
D
Jakus
J
J
Pettigrew
G W
GW
D000218:Adamantane / Q000737:chemistry; D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry; D006358:Hot Temperature; D008024:Ligands; D011312:Pressure; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D003505:Cyclodextrins; D008024:Ligands; D011506:Proteins; D014867:Water; D000218:Adamantane