Diffusion and Viscosity in Mixed Protein Solutions

The viscosity and diffusion properties of crowded protein systems\nwere investigated with molecular dynamics simulations of SH3 mixtures\nwith different crowders, and results were compared with experimental\ndata. The simulations accurately reproduced experimental trends across\na wide range of protein concentrations, including highly crowded environments\nup to 300 g/L. Notably, viscosity increased with crowding but varied\nlittle between different crowder types, while diffusion rates were\nsignificantly reduced depending on protein–protein interaction\nstrength. Analysis using the Stokes–Einstein relation indicated\nthat the reduction in diffusion exceeded what was expected from viscosity\nchanges alone, with the additional slow-down attributable to transient\ncluster formation driven by weakly attractive interactions. Contact\nkinetics analysis further revealed that longer-lived interactions\ncontributed more significantly to reduced diffusion rates than short-lived\ninteractions. This study also highlights the accuracy of current computational\nmethodologies for capturing the dynamics of proteins in highly concentrated\nsolutions and provides insights into the molecular mechanisms affecting\nprotein mobility in crowded environments.