Calculation of absolute binding free energies between the hERG channel and structurally diverse drugs.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 11 2019
12 11 2019
Historique:
received:
27
08
2019
accepted:
28
10
2019
entrez:
14
11
2019
pubmed:
14
11
2019
medline:
13
11
2020
Statut:
epublish
Résumé
The human ether-a-go-go-related gene (hERG) encodes a voltage-gated potassium channel that plays an essential role in the repolarization of action potentials in cardiac muscle. However, various drugs can block the ion current by binding to the hERG channel, resulting in potentially lethal cardiac arrhythmia. Accordingly, in silico studies are necessary to clarify the mechanisms of how these drugs bind to the hERG channel. Here, we used the experimental structure of the hERG channel, determined by cryo-electron microscopy, to perform docking simulations to predict the complex structures that occur between the hERG channel and structurally diverse drugs. The absolute binding free energies for the models were calculated using the MP-CAFEE method; calculated values were well correlated with experimental ones. By applying the regression equation obtained here, the affinity of a drug for the hERG channel can be accurately predicted from the calculated value of the absolute binding free energy.
Identifiants
pubmed: 31719645
doi: 10.1038/s41598-019-53120-6
pii: 10.1038/s41598-019-53120-6
pmc: PMC6851376
doi:
Substances chimiques
Ether-A-Go-Go Potassium Channels
0
Potassium Channel Blockers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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