Effect of protein-protein interactions and solvent viscosity on the rotational diffusion of proteins in crowded environments.

Abstract

The rotational diffusion of a protein in the presence of protein crowder molecules was analyzed via computer simulations. Cluster formation as a result of transient intermolecular contacts was identified as the dominant effect for reduced rotational diffusion upon crowding. The slow-down in diffusion was primarily correlated with direct protein-protein contacts rather than indirect interactions via shared hydration layers. But increased solvent viscosity due to crowding contributed to a lesser extent. Key protein-protein contacts correlated with a slow-down in diffusion involve largely interactions between charged and polar groups suggesting that the surface composition of a given protein and the resulting propensity for forming interactions with surrounding proteins in a crowded cellular environment may be the major determinant of its diffusive properties.