Competitive ligand binding kinetics to linear polymers

TL;DR

This paper develops a comprehensive kinetic model for competitive ligand binding to linear polymers, emphasizing the significant impact of ligand size over affinity or cooperativity in binding efficiency.

Contribution

It introduces a general theoretical framework for understanding competitive ligand binding kinetics on polymers, incorporating ligand size, binding rates, and cooperativity.

Findings

Ligand size greatly influences competitive binding outcomes.

Large ligands are more inhibited by smaller ligands due to spatial constraints.

Ligands with multiple binding modes are more effective in lower modes if binding energies are similar.

Abstract

Different types of ligands compete in binding to polymers with different consequences for the physical and chemical properties of the resulting complex. Here, we derive a general kinetic model for the competitive binding kinetics of different types of ligands to a linear polymer, using the McGhee and von Hippel detailed binding site counting procedure. The derived model allows the description of the competitive binding process in terms of the size of the ligand, binding and release rates, and cooperativity parameters. We illustrate the implications of the general theory showing the equations for the competitive binding of two ligands. The size of the ligand, given by the number of monomers occluded, is shown to have a great impact in competitive binding. Ligands requiring a large available gap for binding are strongly inhibited by smaller ligands. Ligand size then has a leading role compared to binding affinity or cooperativity. For ligands that can bind in different modes (i.e., different number of monomers), this implies that they are more effective in covering or passivating the polymer in lower modes, if the different modes have similar binding energies.