Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations.
Journal
Journal of chemical information and modeling
ISSN: 1549-960X
Titre abrégé: J Chem Inf Model
Pays: United States
ID NLM: 101230060
Informations de publication
Date de publication:
08 05 2023
08 05 2023
Historique:
medline:
9
5
2023
pubmed:
14
4
2023
entrez:
13
4
2023
Statut:
ppublish
Résumé
The residence time (RT), the time for which a drug remains bound to its biological target, is a critical parameter for drug design. The prediction of this key kinetic property has been proven to be challenging and computationally demanding in the framework of atomistic simulations. In the present work, we setup and applied two distinct metadynamics protocols to estimate the RTs of muscarinic M3 receptor antagonists. In the first method, derived from the conformational flooding approach, the kinetics of unbinding is retrieved from a physics-based parameter known as the acceleration factor α (i.e., the running average over time of the potential deposited in the bound state). Such an approach is expected to recover the absolute RT value for a compound of interest. In the second method, known as the
Identifiants
pubmed: 37053454
doi: 10.1021/acs.jcim.3c00042
pmc: PMC10170513
doi:
Substances chimiques
Receptor, Muscarinic M3
0
Ligands
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2842-2856Références
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