Li Hongli, Han Binming, Zhang Moxin, Hu Guorong, Li Jingyuan
Zhejiang Province Key Laboratory of Quantum Technology and Device, School of Physics, Zhejiang University, Zheda Road 38, Hangzhou 310027, China.
J Phys Chem B. 2025 Jul 10;129(27):6786-6793. doi: 10.1021/acs.jpcb.5c01831. Epub 2025 Jun 26.
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.
内在无序蛋白（IDPs）在无膜细胞器的形成中起着关键作用。IDPs扩散的降低与凝聚物的稳定性以及包括相分离和分子识别在内的相关生物学过程有关。在此，我们采用分子动力学模拟来研究LAF-1 RGG结构域的扩散动力学及其与溶剂环境的相互作用。我们的结果表明，即使IDPs相隔很远，它们之间水分子的结构有序性也会显著增强。广泛的结构有序伴随着IDPs之间大量水分子扩散动力学的减慢。IDPs对水分子的这些影响可归因于无序构象中带电残基的高度富集，这些残基可与水合水形成强氢键，并促进这些IDPs之间大量水分子氢键网络的形成。事实上，IDPs之间水有序比例的增加和水扩散的减慢意味着相当于IDPs之间溶剂环境冷却18K的效果。因此，即使IDPs之间没有链间接触，IDPs的有效粘度也会显著增加并减缓其扩散。
