Effect of crowding on protein-protein association in diffusion-limited regime

Abstract

In the present paper, we establish a theoretical formalism to study the protein-protein association rate in the framework of diffusion-limited theory. To account for the crowding effect due to the presence of polymer, we particularly take into account the deviation of rotational diffusion of proteins from the Stokes-Einstein-Debye relation. Based on fluid mechanics and depletion theory, a new scaling relation for the retardation factor of the rotational diffusion was proposed. Besides, the crowding-induced interaction energy between the proteins has been also properly introduced into the association rate theory. We apply our theory to calculate the association rate constant of proteins β-lactamase and β-lactamase inhibitor protein in poly(ethylene glycol) solutions. Particular attention is paid to the dependence of the association rate constant on the polymer concentration and polymer molecular weight. The deviation from the simple relation based on Stokes-Einstein approximation is well addressed. We find that our theoretical results show good agreements with the experimental data in the whole concentration region, which demonstrates the validity of our theory.