Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein–Ligand Binding
| Autor: | Kenneth W. Borrelli, Matthew J Grisewood, Phani Ghanakota, Richard A. Friesner, Edward B. Miller, Troast Dawn M, Daniel J. Sindhikara, Robert B. Murphy, Robert Abel, Salma B Rafi, Nicholas A. Boyles, Fabio Ranalli, Tyler Day, Steven V. Jerome, Sayan Mondal, Steven L. Dixon |
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| Rok vydání: | 2021 |
| Předmět: |
010304 chemical physics
Drug discovery Computer science Proteins Protein structure prediction Ligands Ligand (biochemistry) 01 natural sciences Computer Science Applications Molecular Docking Simulation Free energy perturbation Molecular dynamics Docking (molecular) 0103 physical sciences Physical and Theoretical Chemistry Pharmacophore Biological system Protein Binding Protein ligand |
| Zdroj: | Journal of Chemical Theory and Computation. 17:2630-2639 |
| ISSN: | 1549-9626 1549-9618 |
| DOI: | 10.1021/acs.jctc.1c00136 |
| Popis: | We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking, rigid receptor docking, and protein structure prediction with explicit solvent molecular dynamics simulations. This novel methodology in detailed retrospective and prospective testing succeeded to determine protein-ligand binding modes with a root-mean-square deviation within 2.5 Å in over 90% of cross-docking cases. We further demonstrate these predicted ligand-receptor structures were sufficiently accurate to prospectively enable predictive structure-based drug discovery for challenging targets, substantially expanding the domain of applicability for such methods. |
| Databáze: | OpenAIRE |
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