A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction

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dc.contributor.authorPovinelli, Ana Paula Ribeiro
dc.contributor.authorZazeri, Gabriel
dc.contributor.authorJones, Alan M.
dc.contributor.authorCornélio, Marinônio Lopes [UNESP]
dc.contributor.institutionScience and Technology of Mato Grosso
dc.contributor.institutionUniversity of Birmingham
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-03-01T21:12:20Z
dc.date.available2023-03-01T21:12:20Z
dc.date.issued2022-07-01
dc.description.abstractHerein, we elucidate the biophysical aspects of the interaction of an important protein, Interleukin-6 (IL6), which is involved in cytokine storm syndrome, with a natural product with anti-inflammatory activity, piperine. Despite the role of piperine in the inhibition of the transcriptional protein NF-κB pathway responsible for activation of IL6 gene expression, there are no studies to the best of our knowledge regarding the characterisation of the molecular interaction of the IL6-piperine complex. In this context, the characterisation was performed with spectroscopic experiments aided by molecular modelling. Fluorescence spectroscopy alongside van’t Hoff analyses showed that the complexation event is a spontaneous process driven by non-specific interactions. Circular dichroism aided by molecular dynamics revealed that piperine caused local α-helix reduction. Molecular docking and molecular dynamics disclosed the microenvironment of interaction as non-polar amino acid residues. Although piperine has three available hydrogen bond acceptors, only one hydrogen-bond was formed during our simulation experiments, reinforcing the major role of non-specific interactions that we observed experimentally. Root mean square deviation (RMSD) and hydrodynamic radii revealed that the IL6-piperine complex was stable during 800 ns of simulation. Taken together, these results can support ongoing IL6 drug discovery efforts.en
dc.description.affiliationFederal Institute of Education Science and Technology of Mato Grosso
dc.description.affiliationSchool of Pharmacy Institute of Clinical Sciences College of Medical and Dental Sciences University of Birmingham, Edgbaston
dc.description.affiliationDepartamento de Física Instituto de Biociências Letras e Ciências Exatas (IBILCE) UNESP, Rua Cristovão Colombo 2265
dc.description.affiliationUnespDepartamento de Física Instituto de Biociências Letras e Ciências Exatas (IBILCE) UNESP, Rua Cristovão Colombo 2265
dc.identifierhttp://dx.doi.org/10.3390/ijms23147994
dc.identifier.citationInternational Journal of Molecular Sciences, v. 23, n. 14, 2022.
dc.identifier.doi10.3390/ijms23147994
dc.identifier.issn1422-0067
dc.identifier.issn1661-6596
dc.identifier.scopus2-s2.0-85137228705
dc.identifier.urihttp://hdl.handle.net/11449/241599
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.sourceScopus
dc.subjectfluorescence spectroscopy
dc.subjectIL6
dc.subjectInterleukin-6
dc.subjectmolecular biophysics
dc.subjectmolecular docking
dc.subjectpiperine
dc.subjectumbrella sampling
dc.titleA Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interactionen
dc.typeArtigo
unesp.author.orcid0000-0002-3897-5626[3]
unesp.author.orcid0000-0002-0755-8643[4]

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