Performance evaluation of flexible macrocycle docking in AutoDock.
autodock
docking
macrocycles
Journal
QRB discovery
ISSN: 2633-2892
Titre abrégé: QRB Discov
Pays: England
ID NLM: 101772102
Informations de publication
Date de publication:
2022
2022
Historique:
received:
04
06
2022
revised:
04
10
2022
accepted:
05
10
2022
medline:
2
8
2023
pubmed:
2
8
2023
entrez:
2
8
2023
Statut:
epublish
Résumé
Macrocycles represent an important class of ligands, both in natural products and designed drugs. In drug design, macrocyclizations can impart specific ligand conformations and contribute to passive permeation by encouraging intramolecular H-bonds. AutoDock-GPU and Vina can model macrocyclic ligands flexibly, without requiring the enumeration of macrocyclic conformers before docking. Here, we characterize the performance of the method for handling macrocyclic compounds, which is implemented and the default behaviour for ligand preparation with our ligand preparation pipeline, Meeko. A pseudoatom is used to encode bond geometry and produce an anisotropic closure force for macrocyclic rings. This method is evaluated on a diverse set of small molecule and peptide macrocycles, ranging from 7- to 33-membered rings, showing little accuracy loss compared to rigid redocking of the X-ray macrocycle conformers. This suggests that for conformationally flexible macrocycles with unknown binding modes, this method can be effectively used to predict the macrocycle conformation.
Identifiants
pubmed: 37529284
doi: 10.1017/qrd.2022.18
pii: S2633289222000187
pmc: PMC10392634
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e18Informations de copyright
© The Author(s) 2022.
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