Studying protein assembly with reversible Brownian dynamics of patchy particles

TL;DR

This paper presents a computational method using reversible Brownian dynamics of patchy particles to simulate protein assembly, accurately capturing the effects of diffusion and reversible reactions on complex formation.

Contribution

It introduces a novel simulation scheme that ensures detailed balance and models reversible protein assembly with anisotropic interactions and on-the-fly diffusion calculations.

Findings

Simulation results match macroscopic kinetic models

The method accurately captures diffusion and reaction processes

Reversible assembly dynamics are effectively modeled

Abstract

Assembly of protein complexes like virus shells, the centriole, the nuclear pore complex or the actin cytoskeleton is strongly determined by their spatial structure. Moreover it is becoming increasingly clear that the reversible nature of protein assembly is also an essential element for their biological function. Here we introduce a computational approach for the Brownian dynamics of patchy particles with anisotropic assemblies and fully reversible reactions. Different particles stochastically associate and dissociate with microscopic reaction rates depending on their relative spatial positions. The translational and rotational diffusive properties of all protein complexes are evaluated on-the-fly. Because we focus on reversible assembly, we introduce a scheme which ensures detailed balance for patchy particles. We then show how the macroscopic rates follow from the microscopic ones. As an instructive example, we study the assembly of a pentameric ring structure, for which we find excellent agreement between simulation results and a macroscopic kinetic description without any adjustable parameters. This demonstrates that our approach correctly accounts for both the diffusive and reactive processes involved in protein assembly.