Entropy-enthalpy Compensation of Biomolecular Systems in Aqueous Phase: a Dry Perspective.

We survey thermodynamic measurements on processes involving biological macromolecules in aqueous solution, which illustrate well the ubiquitous phenomenon of entropy-enthalpy compensation. The processes include protein folding/unfolding and ligand binding/unbinding, with compensation temperatures varying by about 50 K around an average near 293 K. We show that incorporating both near-exact entropy-enthalpy compensation (due to solvent relaxation) and multi-excitation entropy (from vibrational quanta) leads to a compensation temperature in water of about 230 K. We illustrate a general procedure for subtracting solvent and environment-related terms to determine the bare Gibbs free energy changes of chemical processes.