Crowding induced entropy-enthalpy compensation in protein association equilibria

TL;DR

This paper develops a statistical mechanical theory to predict how macromolecular crowding influences protein association equilibria, considering both excluded volume and attractive interactions, with predictions validated against simulations.

Contribution

It introduces a comprehensive theory that accounts for both repulsive and attractive interactions in crowding effects on protein binding, validated by simulation data.

Findings

Attractive interactions counteract excluded volume effects.

Predicted binding free energies match simulation results.

Critical attraction strength is nearly independent of crowder packing fraction.

Abstract

A statistical mechanical theory is presented to predict the effects of macromolecular crowding on protein association equilibria, accounting for both excluded volume and attractive interactions between proteins and crowding molecules. Predicted binding free energies are in excellent agreement with simulation data over a wide range of crowder sizes and packing fraction. It is shown that attractive interactions between proteins and crowding agents counteract the stabilizing effects of excluded volume interactions. A critical attraction strength, for which there is no net effect of crowding, is almost independent of the crowder packing fraction.