蛋白折叠中的暂态结构与表面水分子慢尺度动力学

蛋白表面水的慢尺度动力学行为往往被认为与蛋白的结构稳定性、功能以及折叠过程有关, 但在分子水平上, 还不清楚水分子的慢尺度动力学如何参与蛋白折叠过程. 以Trp-cage蛋白作为个案, 本文利用40条100 ns(总长4 μs)的全原子分子动力学轨迹,分析了蛋白折叠过程中蛋白表面水分子的停留行为，并探究影响蛋白表面水分子慢尺度行为的微观因素. 结果发现, 即使在蛋白折叠过程中蛋白拓扑结构变化很大, 残基之间也会形成稳定的局部暂态结构. 这些结构为水分子提供饱和、稳定的氢键, 通过与水分子之间的极性相互作用, 以及凹形的几何结构, 约束水分子长时停留, 我们称之为“停留中心”. 停留中心的形成是引起水分子慢尺度行为的重要因素. 另外, 停留中心的分布与蛋白折叠的进程有密切关系, 特别地, 在折叠轨迹中, 疏水核周围的残基组成了一个主要的停留中心. 研究结果不但有助于解释水分子慢尺度特征行为的来源, 还可以为实验中通过研究水分子在蛋白附近的慢尺度行为, 揭示蛋白折叠过程中的关键步骤提供一些启发.

Intermediate Structure and Slow Hydration Water Dynamics in Protein Folding Process

The slow dynamics of hydration water has long been recognized as a major determinant of protein stability, function, and folding. However, an atomic level mechanism is still lacking on the origin of the slow dynamics of hydration water and how it is involved in protein folding. Using forty 100-ns all-atom molecular dynamics simulations of the Trp-cage mini-protein as a case study, we analyzed the dynamics of hydration water in the protein folding process to explore the origin of the slow dynamics of hydration water in detail. During the folding process, even if the topological structure of the protein changed greatly, there were certain intermediate protein structures where the hydration water showed slow dynamics. By providing rich hydrogen bond connections and the advantage of a convex topology these structures enslave water molecules for very long time and we refer to these as“residence centers”. Residence centers are the possible origin of the slow dynamics of hydration water. Additionally, the distribution of residence centers is closely related to the folding process. In folded trajectories, the residues around the hydrophobic core form a main residence center. These results are helpful in explaining the origin of the slow water dynamics on protein surfaces and may provide some insight into further experimental study to probe important intermediate structures during the process of protein folding by capturing slowhydration water dynamics.