Drug binding dynamics of the dimeric SARS-CoV-2 main protease, determined by molecular dynamics simulation.
Sci Rep
; 10(1): 16986, 2020 10 12.
Article
en En
| MEDLINE
| ID: mdl-33046764
ABSTRACT
We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein-ligand complexes and suggest the possibilities of further drug optimisations.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neumonía Viral
/
Cisteína Endopeptidasas
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Proteínas no Estructurales Virales
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Inhibidores de la Proteasa del VIH
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Infecciones por Coronavirus
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Reposicionamiento de Medicamentos
/
Betacoronavirus
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón