Molecular modeling simulation studies reveal new potential inhibitors against HPV E6 protein

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dc.contributor.authorRicci-López, Joel
dc.contributor.authorVidal-Limon, Abraham
dc.contributor.authorZunñiga, Matías
dc.contributor.authorJiménez, Verónica A.
dc.contributor.authorAlderete, Joel B.
dc.contributor.authorBrizuela, Carlos A.
dc.contributor.authorAguila, Sergio
dc.date.accessioned2023-08-08T17:14:38Z
dc.date.available2023-08-08T17:14:38Z
dc.date.issued2019-03
dc.descriptionIndexación Scopuses
dc.description.abstractHigh-risk strains of human papillomavirus (HPV) have been identified as the etiologic agent of some anogenital tract, head, and neck cancers. Although prophylactic HPV vaccines have been approved; it is still necessary a drug-based treatment against the infection and its oncogenic effects. The E6 oncoprotein is one of the most studied therapeutic targets of HPV, it has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6 can promote the degradation of p53, a tumor suppressor protein, through the interaction with the cellular ubiquitin ligase E6AP. Therefore, preventing the formation of the E6-E6AP complex is one of the main strategies to inhibit the viability and proliferation of infected cells. Herein, we propose an in silico pipeline to identify small-molecule inhibitors of the E6-E6AP interaction. Virtual screening was carried out by predicting the ADME properties of the molecules and performing ensemble-based docking simulations to E6 protein followed by binding free energy estimation through MM/PB(GB)SA methods. Finally, the top-three compounds were selected, and their stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction was corroborated by molecular dynamics simulation. Therefore, this pipeline and the identified molecules represent a new starting point in the development of anti-HPV drugs.es
dc.identifier.citationPLoS ONE Volume 14, Issue 3 March 2019 Article number e0213028es
dc.identifier.doi10.1371/journal.pone.0213028en
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/52314
dc.language.isoenes
dc.publisherPLoS ONEes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.esen
dc.subjectAntiviral Agentses
dc.subjectDNA-Binding Proteinses
dc.subjectDrug Developmentes
dc.subjectHuman papillomavirus 16es
dc.subjectHumanses
dc.subjectMolecular Docking Simulationses
dc.titleMolecular modeling simulation studies reveal new potential inhibitors against HPV E6 proteines
dc.typeArtículoes
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