A molecular reconstruction approach to site-based 3D-RISM and comparison to GIST hydration thermodynamic maps in an enzyme active site
| Autor: | Takeshi Yamazaki, Tyler Luchko, Michael K. Gilson, Tom Kurtzman, Crystal N. Nguyen, Andriy Kovalenko, David A. Case |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Hydrogen
Entropy Molecular Conformation 01 natural sciences Molecular dynamics Catalytic Domain Statistical physics Entropy (energy dispersal) Materials Free Energy Physics Multidisciplinary 010304 chemical physics biology Chemical Reactions Enzymes Solutions Chemistry Physical Sciences Molecular Density Probability distribution Medicine Thermodynamics Research Article Chemical Elements Statistical Distributions Science Materials Science chemistry.chemical_element Solvation Molecular Dynamics Simulation 010402 general chemistry Molecular recognition 0103 physical sciences Solutes Binding Sites Active site Water Probability Theory 0104 chemical sciences Oxygen chemistry Mixtures biology.protein Solvents Mathematics |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 7, p e0219473 (2019) |
| Popis: | Computed, high-resolution, spatial distributions of solvation energy and entropy can provide detailed information about the role of water in molecular recognition. While grid inhomogeneous solvation theory (GIST) provides rigorous, detailed thermodynamic information from explicit solvent molecular dynamics simulations, recent developments in the 3D reference interaction site model (3D-RISM) theory allow many of the same quantities to be calculated in a fraction of the time. However, 3D-RISM produces atomic-site, rather than molecular, density distributions, which are difficult to extract physical meaning from. To overcome this difficulty, we introduce a method to reconstruct molecular density distributions from atomic-site density distributions. Furthermore, we assess the quality of the resulting solvation thermodynamics density distributions by analyzing the binding site of coagulation Factor Xa with both GIST and 3D-RISM. We find good qualitative agreement between the methods for oxygen and hydrogen densities as well as direct solute-solvent energetic interactions. However, 3D-RISM predicts lower energetic and entropic penalties for moving water from the bulk to the binding site. |
| Databáze: | OpenAIRE |
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