Theoretical Aspects of DNA-protein Interactions: Co-Operative and Non-Co-operative Binding of Large Ligands to a One-Dimensional Homogeneous Lattice.

The interaction of proteins binding non-specifically to DNA, as well as the properties of many other interacting ligand-lattice systems important in molecular biology, requires a fundamentally different type of theoretical analysis than that provided by the classical Scatchard independent-binding-site treatment. Exact and relatively simple equations describing the binding of both non-interacting and interacting (co-operative) ligands to a homogeneous one-dimensional lattice are derived in terms of ligand site size, intrinsic binding constant and ligand-ligand co-operativity (equations (10) and (15) in the text). The mathematical approach is based on simple conditional probabilities, and reveals some largely unrecognized characteristics of such lattice binding systems. The results indicate that the binding of any non-interacting ligand covering more than one lattice residue results in non-linear (convex downward) Scatchard plots. The introduction of positive ligand-ligand co-operativity antagonizes this non-linearity, and eventually leads to plots of the opposite curvature. The maxima, limiting slopes, and intercepts of such plots can be used to estimate the required binding parameters. The method can be extended to systems involving heterogeneous ligands, and some types of heterogeneous lattices. Procedures for applying the method to a variety of interacting systems are presented, and a preliminary analysis is carried out for some selected sets of data from the literature.