title: Atomic detail brownian dynamics simulations of concentrated protein solutions with a mean field treatment of hydrodynamic interactions.
abstract: High macromolecular concentrations are a distinguishing feature of living organisms. Understanding how the high concentration of solutes affects the dynamic properties of biological macromolecules is fundamental for the comprehension of biological processes in living systems. In this paper, we describe the implementation of mean field models of translational and rotational hydrodynamic interactions into an atomically detailed many-protein brownian dynamics simulation method. Concentrated solutions (30-40% volume fraction) of myoglobin, hemoglobin A, and sickle cell hemoglobin S were simulated, and static structure factors, oligomer formation, and translational and rotational self-diffusion coefficients were computed. Good agreement of computed properties with available experimental data was obtained. The results show the importance of both solvent mediated interactions and weak protein-protein interactions for accurately describing the dynamics and the association properties of concentrated protein solutions. Specifically, they show a qualitative difference in the translational and rotational dynamics of the systems studied. Although the translational diffusion coefficient is controlled by macromolecular shape and hydrodynamic interactions, the rotational diffusion coefficient is affected by macromolecular shape, direct intermolecular interactions, and both translational and rotational hydrodynamic interactions.
authors.affiliation: Heidelberg Institute for Theoretical Studies (HITS) gGmbH, Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany. paolo.mereghetti@h-its.org
authors.forename: Paolo
authors.initials: P
authors.lastname: Mereghetti
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Wade
mesh_terms: D000818:Animals; D004058:Diffusion; D006441:Hemoglobin A / Q000737:chemistry*; D006451:Hemoglobin, Sickle / Q000737:chemistry*; D006736:Horses; D006801:Humans; D057446:Hydrodynamics; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry*
chemical_list: D006451:Hemoglobin, Sickle; D009211:Myoglobin; D006441:Hemoglobin A