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Site-specific hydration dynamics of globular proteins and the role of constrained water in solvent exchange with amphiphilic cosolvents.

ABSTRACT: The thermodynamic driving forces for protein folding, association, and function are often determined by protein-water interactions. With a novel covalently bound labeling approach, we have used sensitive vibrational probes, site-selectively conjugated to two lysozyme variants-in conjunction with ultrafast two-dimensional infrared (2D-IR) spectroscopy-to investigate directly the protein-water interface. By probing alternatively a topologically flat, rigid domain and a flexible domain, we find direct experimental evidence for spatially heterogeneous hydration dynamics. The hydration environment around globular proteins can vary from exhibiting bulk-like hydration dynamics to dynamically constrained water, which results from stifled hydrogen bond switching dynamics near extended hydrophobic surfaces. Furthermore, we leverage preferential solvation exchange to demonstrate that the liberation of dynamically constrained water is a sufficient driving force for protein-surface association reactions. These results provide an intuitive picture of the dynamic aspects of hydrophobic hydration of proteins, illustrating an essential function of water in biological processes.

SUBMITTER: King JT

PROVIDER: S-EPMC3422398 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Site-specific hydration dynamics of globular proteins and the role of constrained water in solvent exchange with amphiphilic cosolvents.

King John T JT Arthur Evan J EJ Brooks Charles L CL Kubarych Kevin J KJ

The journal of physical chemistry. B 20120507 19

The thermodynamic driving forces for protein folding, association, and function are often determined by protein-water interactions. With a novel covalently bound labeling approach, we have used sensitive vibrational probes, site-selectively conjugated to two lysozyme variants-in conjunction with ultrafast two-dimensional infrared (2D-IR) spectroscopy-to investigate directly the protein-water interface. By probing alternatively a topologically flat, rigid domain and a flexible domain, we find dir ...[more]

PMID: 22530969

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Project description:The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently reported simulations indicating a correlation between regional hydration dynamics and the structure of the solvation layer around different regions of the enzyme Candida antarctica lipase B, wherein the radial distribution function (RDF) was used to calculate the pairwise entropy, providing a link between dynamics (diffusion) and thermodynamics (excess entropy) known as Rosenfeld scaling. Regions with higher RDF values/peaks in the hydration layer (the first peak, within 6 Å of the protein surface) have faster diffusion in the hydration layer. The finding thus hinted at a handle for rapid evaluation of hydration dynamics at different regions on the protein surface in molecular dynamics simulations. Such an approach may move the analysis of hydration dynamics from a specialized venture to routine analysis, enabling an informatics approach to evaluate the role of hydration dynamics in biomolecular function. This paper first confirms that the correlation between regional diffusive dynamics and hydration layer structure (via water center of mass around protein side-chain atom RDF) is observed as a general relationship across a set of proteins. Second, it seeks to devise an approach for rapid analysis of hydration dynamics, determining the minimum amount of information and computational effort required to get a reliable value of hydration dynamics from structural data in MD simulations based on the protein-water RDF. A linear regression model using the integral of the hydration layer in the water-protein RDF was found to provide statistically equivalent apparent diffusion coefficients at the 95% confidence level for a set of 92 regions within five different proteins. In summary, RDF analysis of 10 ns of data after simulation convergence is sufficient to accurately map regions of fast and slow hydration dynamics around a protein surface. Additionally, it is anticipated that a quick look at protein-water RDFs, comparing peak heights, will be useful to provide a qualitative ranking of regions of faster and slower hydration dynamics at the protein surface for rapid analysis when investigating the role of solvent dynamics in protein function.

Dataset Information

Site-specific hydration dynamics of globular proteins and the role of constrained water in solvent exchange with amphiphilic cosolvents.

Publications

Site-specific hydration dynamics of globular proteins and the role of constrained water in solvent exchange with amphiphilic cosolvents.

Similar Datasets

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