Multiple Binding of Ligands to a Linear Biopolymer

Abstract

Publisher Summary Many biological processes involve cooperative binding of several different protein ligands to linear biopolymers (such as DNA, actin, and microtubules). If each subunit (monomer) of the biopolymer has only one ligand-binding site, the binding is purely competitive and cooperative binding phenomena are derived mainly from nearest-neighbor ligand–ligand interactions. This kind of binding is referred to as the ‘‘single-binding’’ type. On the other hand, in ‘‘multiple-binding’’ systems in which each subunit of the biopolymer contains two or more binding sites, such that more than one ligand can bind to the same subunit simultaneously, the cooperative binding of one ligand may be modulated allosterically by the other ligand. For example, binding of myosin subfragment 1 (S-1) molecules to a bare actin is known to be noncooperative. But, when the actin is prebound with tropomyosin–troponin molecules, the binding of S-1 becomes cooperative. Theoretical treatment of cooperative binding of ligands to linear biopolymers is an interesting biophysical problem and has attracted considerable attention. However, most of the formalisms developed so far are concentrated on the ‘‘single-binding’’ model. This chapter introduces a formalism that can be used to treat not only single-binding systems, but also multiple-binding systems. Instead of discussing the theoretical basis of the formalism, this chapter uses a simple two-ligand multiple-binding system to illustrate how to carry out the evaluation of the secular equation and the binding isotherms. The purpose is to present the general methodology of the formalism, so that one may be able to modify or extend when needed.