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SARS-COV-2 Mpro conformational changes induced by covalently bound ligands.
Ferreira, Glaucio Monteiro; Kronenberger, Thales; Tonduru, Arun Kumar; Hirata, Rosario Dominguez Crespo; Hirata, Mario Hiroyuki; Poso, Antti.
Afiliação
  • Ferreira GM; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
  • Kronenberger T; Department of Oncology and Pneumonology, Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
  • Tonduru AK; Department of Oncology and Pneumonology, Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany.
  • Hirata RDC; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
  • Hirata MH; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
  • Poso A; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
J Biomol Struct Dyn ; 40(22): 12347-12357, 2022.
Article em En | MEDLINE | ID: mdl-34516349
SARS-CoV-2's main protease (Mpro) interaction with ligands has been explored with a myriad of crystal structures, most of the monomers. Nonetheless, Mpro is known to be active as a dimer but the relevance of the dimerization in the ligand-induced conformational changes has not been fully elucidated. We systematically simulated different Mpro-ligand complexes aiming to study their conformational changes and interactions, through molecular dynamics (MD). We focused on covalently bound ligands (N1 and N3, ∼9 µs per system both monomers and dimers) and compared these trajectories against the apostructure. Our results suggest that the monomeric simulations led to an unrealistically flexible active site. In contrast, the Mpro dimer displayed a stable oxyanion-loop conformation along the trajectory. Also, ligand interactions with residues His41, Gly143, His163, Glu166 and Gln189 are postulated to impact the ligands' inhibitory activity significantly. In dimeric simulations, especially Gly143 and His163 have increased interaction frequencies. In conclusion, long-timescale MD is a more suitable tool for exploring in silico the activity of bioactive compounds that potentially inhibit the dimeric form of SARS-CoV-2 Mpro.Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido