Thermodynamics of ligand binding to proteins

The phenomenological characterization of binding reactions is described by the amount of chemical ligand bound along with concomitant and physical effects of heat and volume change. Binding measurements, calorimetry, and dilatometry provide a direct route for the evaluation of relevant reaction parameters. Indirectly the study of the response to temperature, pressure, and ligand chemical potentials yields the same information. From a theoretical view the functional chemistry of biological molecules is broadly depicted by a stoichiometrically based binding partition function as suggested by Wyman (Adv. Protein Chem., 19. 224-286 (1964)). Derivatives of this function provide a direct link to experimental measurements and provide the basis for the quantitative description of homotropic cooperativity and heterotropic linkage. The formulation of the partition function can when appropriate be given for allosteric (conformational) and polysteric (aggregational) systems, with the inclusion of binding effects involving chemical, volume, and enthalpy change. Applications of these concepts are drawn from recent studies of ligand binding to hemoglobin and hemocyanin.