Influence of Binding Site Affinity Patterns on Binding of Multivalent Polymers

Abstract

© 2020 American Chemical Society. Using inspiration from biology, we can leverage multivalent binding interactions to enhance weak, monovalent binding between molecules. While most previous studies have focused on multivalent binders with uniform binding sites, new synthetic polymers might find it desirable to have multiple binding moieties along the chain. Here, we probe how patterning of heterogeneous binding sites along a polymer chain controls the binding affinity of a polymer using a reactive Brownian dynamics scheme. Unlike monovalent binders that are pattern-agnostic, we find that divalent binding is dependent on both the polymer pattern and binding target concentration. For dilute targets, blocky polymers provide high local concentrations of high-affinity sites, but at high target concentrations, competition for binding sites makes alternating polymers the strongest binders. Subsequently, we show that random copolymers are robust to target concentration fluctuations. These results will assist in the rational design of multivalent polymer therapeutics and materials.