(102b) Coupling Between Protein and Solvent Dynamics in Crowded and Non-Aqueous Environments

In this work, we report the results of a series of all-atom molecular dynamics simulations that are designed to probe the coupling between solvent and protein dynamics in non-conventional environments. Two types of environments are explored, crowded environment and hexane organic solvent. In both cases, simulations with a broad range of water content in the protein system are performed. The protein that we focus on in this work is subtilisin, whose enzyme activity has been measured under a variety of different environments. It has been shown that the activity of subtilisin strongly depends on solvation condition such as water content and that the dynamics of water is strongly correlated with the dynamics of protein and enzyme activity. Our goal is to provide molecular insight to explain these experimental observations. First, we quantify the heterogeneity of water dynamics in different conditions. We clearly see the coexistence of water molecules that are strongly bound to protein and mobile water molecules in different simulations. We also identify loop motions of subtilisin whose dynamics are very sensitive to solvation conditions. These motions modulate the exposure of the active site of subtilisin and our results can also be used to explain why subtilisin activity is reduced by several orders of magnitude in an environment with low-water content.