Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking
| datacite.creator | Valdés Albuernes, Jorge Luis | |
| datacite.creator | Díaz Pico, Erbio | |
| datacite.creator | Alfaro, Sergio | |
| datacite.creator | Caballero, Julio | |
| datacite.date.issued | 2024 | |
| datacite.identifier | DOI | |
| datacite.identifier.doi | 10.3389/fmolb.2024.1374364 | |
| datacite.identifier.issn | 2296-889X | |
| datacite.identifier.orcid | 0000-0003-0182-1444 | |
| datacite.identifier.wosid | WOS:001198857700001 | |
| datacite.rights | Acceso abierto | |
| datacite.subject | Papain-like protease | |
| datacite.subject | PLpro inhibitors | |
| datacite.subject | SARS-CoV-2 | |
| datacite.subject | Docking energy-activity correlation | |
| datacite.subject | Flexible molecular docking | |
| datacite.subject | Molecular dynamics | |
| datacite.title | Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking | |
| dc.date.accessioned | 2024-10-15T20:48:48Z | |
| dc.date.available | 2024-10-15T20:48:48Z | |
| dc.description.abstract | The papain-like protease (PLpro) found in coronaviruses that can be transmitted from animals to humans is a critical target in respiratory diseases linked to Severe Acute Respiratory Syndrome (SARS-CoV). Researchers have proposed designing PLpro inhibitors. In this study, a set of 89 compounds, including recently reported 2-phenylthiophenes with nanomolar inhibitory potency, were investigated as PLpro noncovalent inhibitors using advanced molecular modeling techniques. To develop the work with these inhibitors, multiple structures of the SARS-CoV-2 PLpro binding site were generated using a molecular sampling method. These structures were then clustered to select a group that represents the flexibility of the site. Subsequently, models of the protein-ligand complexes were created for the set of inhibitors within the chosen conformations. The quality of the complex models was assessed using LigRMSD software to verify similarities in the orientations of the congeneric series and interaction fingerprints to determine the recurrence of chemical interactions. With the multiple models constructed, a protocol was established to choose one per ligand, optimizing the correlation between the calculated docking energy values and the biological activities while incorporating the effect of the binding site's flexibility. A strong correlation (R2 = 0.922) was found when employing this flexible docking protocol. | |
| dc.description.pages | 15 p. | |
| dc.identifier.folio | 1210138 | |
| dc.identifier.uri | https://repositorio.utalca.cl/repositorio/handle/1950/14301 | |
| dc.language | Inglés | |
| dc.publisher | Frontiers | |
| dc.relation.uri | https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1374364/full | |
| dc.source | Frontiers in Molecular Biosciences | |
| oaire.citationTitle | Frontiers in Molecular Biosciences | |
| oaire.fundingReference | The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by FONDECYT Regular grant number 1210138 (JC). | |
| oaire.licenseCondition | http://creativecommons.org/licenses/by/4.0/ | |
| oaire.licenseCondition.uri | http://creativecommons.org/licenses/by/4.0/ | |
| oaire.resourceType | Artículo de Revista | |
| oaire.version | Versión Publicada | |
| utalca.catalogador | PAG | |
| utalca.facultad | Universidad de Talca (Chile). Facultad de Ingeniería. Centro de Bioinformática Simulación y Modelado. | |
| utalca.idcarga | pag15102024 | |
| utalca.index | Artículo indexado en Web of Science | |
| utalca.index | Artículo indexado en Scopus | |
| utalca.informaciondegenero | Hombre | |
| utalca.ods | Salud y bienestar | |
| utalca.ods | Industria, innovación e infraestructura |
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