Accurate prediction of dynamic protein-ligand binding using P-score ranking
© 2024 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 45(2024), 20 vom: 30. Juni, Seite 1762-1778 |
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| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article P‐score binding pose prediction dynamic average quantum mechanics fragment molecular orbital supervised molecular dynamics Ligands Proteins |
| Zusammenfassung: | © 2024 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC. Protein-ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein-ligand system, solvent-mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein-ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P-score. This is illustrated using six different protein-ligand targets as case studies |
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| Beschreibung: | Date Completed 12.06.2024 Date Revised 12.06.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.27370 |