ABSTRACT

This chapter develops an analytical formalism to describe how macromolecules interact with ligands using statistical thermodynamics, and explores how different types of functional behavior arise. Different binding schemes will be considered, from simple one-to-one binding to multistep binding of several ligands to a macromolecule. Ligand titration curves will be developed as a fundamental graphical representation of macromolecule–ligand interaction. The chapter begins with a simple bimolecular binding reaction of a single ligand x to a single site on macromolecule M. In addition to introducing nomenclature, the chapte uses the example to show some features of different types of binding curves, as well as some practical considerations and complications associated with measuring ligand binding reactions. Fractional saturation is the fraction of macromolecular binding sites that have ligand bound. The chapter develops the framework for modeling multisite equilibria and for determining affinities and interaction energies.