Protein solvent shell structure provides rapid analysis of hydration dynamics

• Published in: Journal of Chemical Information and Modeling
• Main Authors: Dahanayake, Jayangika Niroshani, Shahryari, Elaheh, Roberts, Kirsten M., Heikes, Micah E., Kasireddy, Chandana, Mitchell-Koch, Katie R.
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Chemical Society 2019
• Subjects: Distribution functions; Entropy; Function evaluation; Molecular dynamics; Proteins; Regression analysis; Solvation; Surface diffusion; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10057/16435; https://doi.org/10.1021/acs.jcim.9b00009

Click on the DOI link to access the article (may not be free). 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 ...