The Role of Hydrodynamic Interactions in the Rate of Protein Folding

Abstract

Hydrodynamic interactions (HI) affect the diffusivity of protein dynamics. However, a computationally quantitative assessment of its role in protein folding has been an under explored research field. A lack of HI in molecular dynamics simulations fails to capture the experimentally measured translational and rotational diffusion coefficients when HI is no longer negligible, such as inside a crowded cell. In our study, we incorporated hydrodynamic interactions into the equations of motion from the Brownian dynamics by computing the diffusion correlation matrices between each residue. We used a, structure-based model to investigate the folding of two well studied proteins: chymo-trypsin inhibitor 2 (CI2) and the Src Homology 3 (SH3) domain of alpha-spectrin.For both proteins, we observed that HI increases the folding rate varying from 50% to 5% depending on the free energy barrier height. Furthermore, we measured the diffusion throughout the stages of folding to relate HI effect to the structural differences of these two proteins. Lastly, we compared our simulation results with the folding rates predicted by the Free Energy Landscape Theory. Our theoretical calculations will allow us better develop a computational framework for protein folding in crowded cells.