Abstract:

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.

Key words: Protein folding, Trp-cage, Hydration water, Residence time, Residence center