ABSTRACT

This chapter extends the analytical framework to describe binding using a microscopic, site-oriented approach to ligand binding. It develops microstate versions of step-wise and overall binding constants. By borrowing ideas from topology and graph theory, the chapter shows how the number of stepwise and overall constants relate to each other and to the number of thermodynamic cycle associated with binding. The chapter develops a microscopic description of binding in which the constants describe ligand association to individual sites on a macromolecule. Within the three-site mechanism, the chapter begins with a completely general microscopic description of binding, to illustrate the high level of mechanistic detail that can be represented by the microstate approach. The chapter adapts the identical independent binding model to treat schemes in which sites are independent but have different affinities. It also discusses allostery in ligand binding by discussing two popular models for multisubunit proteins: the MWC model and the KNF model.