How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

Abstract

Solvation is critical for protein structural dynamics. Spectroscopic studies have indicated relationships between protein and solvent dynamics, and rates of gas binding to heme proteins in aqueous solution were previously observed to depend inversely on solution viscosity. In this work, the solvent-compatible enzyme Candida antarctica lipase B, which functions in aqueous and organic solvents, was modeled using molecular dynamics simulations. Data was obtained for the enzyme in acetonitrile, cyclohexane, n-butanol, and tert-butanol, in addition to water. Protein dynamics and solvation shell dynamics are characterized regionally: for each α-helix, β-sheet, and loop or connector region. Correlations are seen between solvent mobility and protein flexibility. So, does local viscosity explain the relationship between protein structural dynamics and solvation layer dynamics? Halle and Davidovic presented a cogent analysis of data describing the global hydrodynamics of a protein (tumbling in solution) that fits a model in which the protein's interfacial viscosity is higher than that of bulk water's, due to retarded water dynamics in the hydration layer (measured in NMR τ2 reorientation times). Numerous experiments have shown coupling between protein and solvation layer dynamics in site-specific measurements. Our data provides spatially-resolved characterization of solvent shell dynamics, showing correlations between regional solvation layer dynamics and protein dynamics in both aqueous and organic solvents. Correlations between protein flexibility and inverse solvent viscosity (1/η) are considered across several protein regions and for a rather disparate collection of solvents. It is seen that the correlation is consistently higher when local solvent shell dynamics are considered, rather than bulk viscosity. Protein flexibility is seen to correlate best with either the local interfacial viscosity or the ratio of the mobility of an organic solvent in a regional solvation layer relative to hydration dynamics around the same region. Results provide insight into the function of aqueous proteins, while also suggesting a framework for interpreting and predicting enzyme structural dynamics in non-aqueous solvents, based on the mobility of solvents within the solvation layer. We suggest that Kramers' theory may be used in future work to model protein conformational transitions in different solvents by incorporating local viscosity effects.

How to Engineer Organic Solvent Resistant Enzymes: Insights from Combined Molecular Dynamics and Directed Evolution Study

“…In previous studies, similar behavior was found for Candida rugose lipase (CRL) that CCl4 rendered the side chains in the hydrophobic substrate binding site of CRL more mobile . These results also confirmed that local protein dynamics are associated with solvents interaction . Thereby, except inhibition and water stripping off, the conformational change caused by the interaction of OSs with residues in the substrate binding cleft could also be another main factor that influences the enzyme activity …”

“…Enzymes generally require some essential water molecules bound to the surface of enzymes to maintain protein structure, dynamics, and function . The addition of water molecules can increase both the kinetics and flexibility of enzymes in OSs . Although water activity (a w ) is an important experimental factor for enzyme activity in non‐aqueous media (e. g., pure OSs), however, it is challenging to predict critical hydration level in polar OSs .…”

Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2

“…Regional differences in hydration dynamics around the protein surface have been connected with molecular recognition events within the protein. The tie between local solvent dynamics and regional protein dynamics (flexibility/stability) may explain protein conformational states, which are dependent on a measure of the local hydration and friction/viscosity parameters [ 52 ].…”

Stochastic Reaction–Diffusion Model of the Binding of Monoclonal Antibodies to CD4 Receptors on the Surface of T Cells

“…At some point, the free energy change is sufficiently negative and stable so that the mAb and the receptor can enter an “induced fit”, during which their conformations change in a coordinated way, to reach an optimal negative free energy. The “induced fit” process is intimately coupled to solvation water dynamics [ 18 ]. Most likely solvation water dynamics is also involved in the process of “sampling the free energy landscape” [ 19 , 20 ].…”