Brownian Dynamics Simulations of Proteins in the Presence of Surfaces: Long-range Electrostatics and Mean-field Hydrodynamics

TL;DR

This paper develops a computational model for simulating protein diffusion and adsorption near surfaces, incorporating long-range electrostatics and hydrodynamics, validated on lysozyme adsorption experiments.

Contribution

The authors introduce a novel approach to include surface effects in Brownian Dynamics simulations with long-range interactions, enhancing modeling accuracy.

Findings

Model recovers experimental adsorption observables

Provides mechanistic insights into protein-surface interactions

Simulates multi-molecule adsorption processes

Abstract

Simulations of macromolecular diffusion and adsorption in confined environments can offer valuable mechanistic insights into numerous biophysical processes. In order to model solutes at atomic detail on relevant time scales, Brownian Dynamics simulations can be carried out with the approximation of rigid body solutes moving through a continuum solvent. This allows the precomputation of interaction potential grids for the solutes, thereby allowing the computationally efficient calculation of forces. However, hydrodynamic and long-range electrostatic interactions cannot be fully treated with grid-based approaches alone. Here, we develop a treatment of both hydrodynamic and electrostatic interactions to include the presence of surfaces by modeling grid-based and long-range interactions. We describe its application to simulate the self-association and many-molecule adsorption of the well-characterized protein Hen Egg-White Lysozyme to mica-like and silica-like surfaces. We find that the computational model can recover a number of experimental observables of the adsorption process and provide insights into their determinants. The computational model is implemented in the Simulation of Diffusional Association (SDA) software package.