Long-Range Water Ordering between Intrinsically Disordered Proteins and Its Impact on Protein Diffusion

Intrinsically disordered proteins (IDPs) play a critical role in the formation of membraneless organelles. The reduced diffusion of IDPs is associated with the stability of condensates and the related biological processes including phase separation and molecular recognition. Here we employ molecular dynamics simulations to investigate the diffusion dynamics of the LAF-1 RGG domains as well as their interplay with the solvent environment. Our results show that the structural ordering of water molecules between IDPs is significantly enhanced, even when the IDPs are well separated. The extensive structural ordering is accompanied by the slowdown in the diffusion dynamics of substantial water between IDPs. These effects of the IDPs on water molecules can be attributed to the high enrichment of charged residues in disordered conformations, which could form strong hydrogen bonds with hydration water and facilitate the formation of the hydrogen bond network of substantial water between these IDPs. In fact, the increase in the proportion of water ordering between IDPs and the slowing down of the water diffusion imply an effect equivalent to an 18 K cooling of the solvent environment between the IDPs. The effective viscosity for IDPs is thus considerably increased and slows their diffusion even when there are no interchain contacts between IDPs.