Striking Effects of Hydrodynamic Interactions on the Simulated Diffusion and Folding of Proteins.

Abstract

Successful modeling of the processes of protein folding and aggregation may ultimately require accurate descriptions of proteins' diffusive characteristics, which are expected to be influenced by hydrodynamic effects; a comprehensive study of the diffusion and folding of 11 model proteins with an established simulation model extended to include hydrodynamic interactions between residues has therefore been carried out. Molecular simulations that neglect hydrodynamic interactions are incapable of simultaneously reproducing the expected experimental translational and rotational diffusion coefficients of folded proteins, drastically underestimating both when reasonable hydrodynamic radii are employed. In contrast, simulations that include hydrodynamic interactions produce diffusion coefficients that match very well with the expected experimental values for translation and rotation and also correctly capture the significant decrease in translational diffusion coefficient that accompanies protein unfolding. These effects are reflected in folding simulations of the same proteins: the inclusion of hydrodynamic interactions accelerates folding by 2-3-fold with the rate enhancement for the association of secondary structure elements exhibiting a strong sensitivity on the sequence-distance between the associating elements.