Entropy connects water structure and dynamics in protein hydration layer

Abstract

The enzyme Candida Antarctica lipase B (CALB) serves here as a model for understanding connections among hydration layer dynamics, solvation shell structure, and protein surface structure. The structure and dynamics of water molecules in the hydration layer were characterized for regions of the CALB surface, divided around each α-helix, β-sheet, and loop structure. Heterogeneous hydration dynamics were observed around the surface of the enzyme, in line with spectroscopic observations of other proteins. Regional differences in the structure of the biomolecular hydration layer were found to be concomitant with variations in dynamics. In particular, it was seen that regions of higher density exhibit faster water dynamics. This is analogous to the behavior of bulk water, where dynamics (diffusion coefficients) are connected to water structure (density and tetrahedrality) by excess (or pair) entropy, detailed in the Rosenfeld scaling relationship. Additionally, effects of protein surface topology and hydrophobicity on water structure and dynamics were evaluated using multiregression analysis, showing that topology has a somewhat larger effect on hydration layer structure-dynamics. Concave and hydrophobic protein surfaces favor a less dense and more tetrahedral solvation layer, akin to a more ice-like structure, with slower dynamics. Results show that pairwise entropies of local hydration layers, calculated from regional radial distribution functions, scale logarithmically with local hydration dynamics. Thus, the Rosenfeld relationship describes the heterogeneous structure-dynamics of the hydration layer around the enzyme CALB. These findings raise the question of whether this may be a general principle for understanding the structure-dynamics of biomolecular solvation.

How Does Solvation Layer Mobility Affect Protein Structural Dynamics?

“…If the relationship holds, then solvation shell engineering could be used for biocatalysts and de novo proteins to enhance protein stability or flexibility (and dynamics-dependent enzymatic rates) in desired regions. Our recent work on the hydration shell of CALB suggests solvent shell structure determines its dynamics, which may aid a rational approach to tuning regional hydration dynamics around biomolecules (Dahanayake and Mitchell-Koch, 2018 ). Work is underway to see if the same relationships hold for organic solvent.…”

“…The density of the hydration layer, in turn, is strongly correlated with water dynamics, which is an entropic effect. Work is underway to carry out similar analysis of solvent shell structure-dynamics relationships for organic solvents, while looking at correlations with various properties of the protein surface structure (Dahanayake and Mitchell-Koch, 2018 ).…”

Proteins in Ionic Liquids: Reactions, Applications, and Futures

“…This structuring, and rearrangement of anionic coordination sphere could also have implications for the nature of the interaction of ions with a protein surface at different water contents. In addition, different surface topologies could also produce differential hydrogen-bond and ion-interaction dynamics (Dahanayake and Mitchell-Koch, 2018), leading to localized effects, individual to each protein and for particular solvation conditions.…”

Temperature-Jump Solution X-ray Scattering Reveals Distinct Motions in a Dynamic Enzyme

“…The ability to dissect individual conformational motions and measure their rates using time-resolved X-ray measurements is important for understanding processes involving complex protein dynamics. Many of these dynamic processes, including allostery (Colombo et al, 1992;Kim et al, 2016;Royer et al, 1996;Salvay et al, 2003) and enzyme catalysis (Decaneto et al, 2017;Fenwick et al, 2018;Grossman et al, 2011;Guha et al, 2005;Leidner et al, 2018), involve extensive reorganization of interactions between the protein and its ordered solvation shell, which are key contributors to the energetics that govern protein motions (Caro et al, 2017;Conti Nibali et al, 2014;Dahanayake and Mitchell-Koch, 2018;Fenimore et al, 2002;Frauenfelder et al, 2007;Gavrilov et al, 2017;Wand and Sharp, 2018). Because X-ray solution scattering experiments report on the structure of a protein and the ordered solvent molecules that constitute its solvation shell (Henriques et al, 2018;Hub, 2018;Svergun et al, 1998;Virtanen et al, 2011), the widespread application of time-resolved SAXS/WAXS experiments will enhance our understanding of how protein motions are driven by solvent dynamics, especially when they can be combined with molecular dynamics simulations to provide atomic scale insight into the underlying structural changes (Arnlund et al, 2014;Berntsson et al, 2017;Brinkmann and Hub, 2016;Takala et al, 2014).…”