Comprehensive 3D-RISM analysis of the hydration of small molecule binding sites in ligand-free protein structures
© 2020 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.
| Publié dans: | Journal of computational chemistry. - 1984. - 41(2020), 28 vom: 30. Okt., Seite 2406-2419 |
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| Auteur principal: | |
| Autres auteurs: | , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2020
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| Accès à la collection: | Journal of computational chemistry |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't distribution functions of water hydration state hydrogen bonds ligand binding statistical mechanical theory of solvation Ligands Proteins Solvents plus... |
| Résumé: | © 2020 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC. Hydration is a critical factor in the ligand binding process. Herein, to examine the hydration states of ligand binding sites, the three-dimensional distribution function for the water oxygen site, gO (r), is computed for 3,706 ligand-free protein structures based on the corresponding small molecule-protein complexes using the 3D-RISM theory. For crystallographic waters (CWs) close to the ligand, gO (r) reveals that several CWs are stabilized by interaction networks formed between the ligand, CW, and protein. Based on the gO (r) for the crystallographic binding pose of the ligand, hydrogen bond interactions are dominant in the highly hydrated regions while weak interactions such as CH-O are dominant in the moderately hydrated regions. The polar heteroatoms of the ligand occupy the highly hydrated and moderately hydrated regions in the crystallographic (correct) and wrongly docked (incorrect) poses, respectively. Thus, the gO (r) of polar heteroatoms may be used to distinguish the correct binding poses |
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| Description: | Date Completed 14.06.2021 Date Revised 14.06.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.26406 |