We are interested in a system composed of a biological macromolecule and a number of ligands, of which the solvent can be considered one, under conditions of temperature and pressure of biological relevance. Our goal is to characterize the behavior of the macromolecule in its interaction with the various components of the system and the rules underlying the mutual interference of physical and chemical variables. In this chapter we deal with the statistical thermodynamic foundations of binding processes and the concepts that form the basis of our treatment.

Postulates and basic ensembles

The physico-chemical properties of a system are defined thermodynamically by a set of macroscopic quantities accessible to experimental measurements (Fermi, 1936; Schrödinger, 1946). If the macromolecule is taken as the system, then all observables reflect properties of the system and the way it is affected by physical and chemical driving forces. A macromolecule in the presence of multiple ligands can be seen as a system existing in a number of distinct energy states, E1, E2, … Er, totally analogous to the energy states of a quantum mechanical system. Each energy state may be coupled to a conformational state of the macromolecule, i.e., a specific arrangement of its secondary, tertiary or quaternary structure.