How Hydrodynamic Interactions affect the Folding Rate of Proteins

Abstract

Hydrodynamic interaction (HI) arises by the solvent flow generated by the movement of a particle that affects other particles. This long-range interaction is particularly important in the dynamics of proteins that are immersed in the crowded milieu of cells. Therefore, there is a need for a computationally and theoretical quantitative evaluation of its role in protein folding. Using coarse-grained molecular simulations and theoretical calculations according to the Energy Landscape Theory of protein folding, we assess the impact of hydrodynamic interaction in the folding of two model proteins, the 64-residue protein chymotrypsin inhibitor 2 (CI2), and the 57-residue alpha-spectrin Src-homology 3 (SH3) domain. In our study, we included hydrodynamic interaction into the equations of motion from Brownian dynamics by computing the diffusion correlation matrices between each residue. We investigated the folding kinetics as well as the thermodynamics of each protein in the presence and in the absence of hydrodynamic interaction. Our results suggest that the impact from hydrodynamic interaction is dependent on the topology of a protein, and temperature.