Controlling the folding and substrate-binding of proteins using polymer brushes

TL;DR

This study uses Monte Carlo simulations to explore how grafted polymer chains influence protein folding and substrate binding, revealing effects of crowding and polymer length on protein stability and binding pathways.

Contribution

It introduces a computational approach to analyze how polymer brushes modulate protein folding and binding, highlighting the role of crowding and polymer length in these processes.

Findings

Polymer chains hinder fully folded proteins during binding.

Crowding agents can favor correct folding and binding configurations.

Free energy changes depend non-monotonically on polymer length.

Abstract

The extent of coupling between the folding of a protein and its binding to a substrate varies from protein to protein. Some proteins have highly structured native states in solution, while others are natively disordered and only fold fully upon binding. In this Letter, we use Monte Carlo simulations to investigate how disordered polymer chains grafted around a binding site affect the folding and binding of three model proteins. The protein that approaches the substrate fully folded is more hindered during the binding process than those whose folding and binding are cooperative. The polymer chains act as localized crowding agents and can select correctly folded and bound configurations in favor of non-specifically adsorbed states. The free energy change for forming all intra-protein and protein-substrate contacts can depend non-monotonically on the polymer length.