A DIRECT MEASURE OF THE CONTRIBUTION OF SOLVENT REORGANIZATION TO THE ENTHALPY OF LIGAND-BINDING

The thermodynamics of association of several binding systems, including protein-carbohydrate, small molecule-small molecule, protein-peptide, and protein-nucleic acid, were evaluated calorimetrically in light and heavy water. In every case, the enthalpy of binding in D2O was decreased relative to that in H2O: the differences range from 400 to 1800 cal mol(-1). A compensating change in Delta S left the free energy of binding virtually unchanged in each case. A strong correlation between the differential enthalpy of binding and Delta C-p for binding was observed, with a slope of 5 K. An analysis of the observed effect utilizing a Born-Haber thermodynamic cycle shows that the measured decrease in enthalpy represents approximately 10% of the binding enthalpy arising from solvent reorganization. For the range of systems investigated, solvent reorganization provides 25-100% of the observed enthalpy of binding.