Titre
Attracting Cavities 2.0: Improving the Flexibility and Robustness for Small-Molecule Docking.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Röhrig, U.F.
Auteure/Auteur
Goullieux, M.
Auteure/Auteur
Bugnon, M.
Auteure/Auteur
Zoete, V.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1549-960X
Statut éditorial
Publié
Date de publication
2023-06-26
Volume
63
Numéro
12
Première page
3925
Dernière page/numéro d’article
3940
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Molecular docking is a computational approach for predicting the most probable position of a ligand in the binding site of a target macromolecule. Our docking algorithm Attracting Cavities (AC) has been shown to compare favorably to other widely used docking algorithms [Zoete, V.; et al. J. Comput. Chem. 2016, 37, 437]. Here we describe several improvements of AC, making the sampling more robust and providing more flexibility for either fast or high-accuracy docking. We benchmark the performance of AC 2.0 using the 285 complexes of the PDBbind Core set, version 2016. For redocking from randomized ligand conformations, AC 2.0 reaches a success rate of 73.3%, compared to 63.9% for GOLD and 58.0% for AutoDock Vina. Due to its force-field-based scoring function and its thorough sampling procedure, AC 2.0 also performs well for blind docking on the entire receptor surface. The accuracy of its scoring function allows for the detection of problematic experimental structures in the benchmark set. For cross-docking, the AC 2.0 success rate is about 30% lower than for redocking (42.5%), similar to GOLD (42.8%) and better than AutoDock Vina (33.1%), and it can be improved by an informed choice of flexible protein residues. For selected targets with a high success rate in cross-docking, AC 2.0 also achieves good enrichment factors in virtual screening.
PID Serval
serval:BIB_38F1AA57EFDC
PMID
DOI données de recherche
10.5281/zenodo.7940100
Date de création
2023-06-08T12:27:32.330Z
Date de création dans IRIS
2025-05-20T19:52:28Z
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Nom
acs.jcim.3c00054.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
6.57 MB
Format
Adobe PDF
PID Serval
serval:BIB_38F1AA57EFDC.P001
URN
urn:nbn:ch:serval-BIB_38F1AA57EFDC7
Somme de contrôle
(MD5):c732b70042939ddd8c83ddbfa7741a34