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A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction
Herein, 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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323498/ https://www.ncbi.nlm.nih.gov/pubmed/35887341 http://dx.doi.org/10.3390/ijms23147994 |
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author | Povinelli, Ana Paula Ribeiro Zazeri, Gabriel Jones, Alan M. Cornélio, Marinônio Lopes |
author_facet | Povinelli, Ana Paula Ribeiro Zazeri, Gabriel Jones, Alan M. Cornélio, Marinônio Lopes |
author_sort | Povinelli, Ana Paula Ribeiro |
collection | PubMed |
description | Herein, 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. |
format | Online Article Text |
id | pubmed-9323498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93234982022-07-27 A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction Povinelli, Ana Paula Ribeiro Zazeri, Gabriel Jones, Alan M. Cornélio, Marinônio Lopes Int J Mol Sci Article Herein, 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. MDPI 2022-07-20 /pmc/articles/PMC9323498/ /pubmed/35887341 http://dx.doi.org/10.3390/ijms23147994 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Povinelli, Ana Paula Ribeiro Zazeri, Gabriel Jones, Alan M. Cornélio, Marinônio Lopes A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title | A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title_full | A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title_fullStr | A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title_full_unstemmed | A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title_short | A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction |
title_sort | computational–experimental investigation of the molecular mechanism of interleukin-6-piperine interaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323498/ https://www.ncbi.nlm.nih.gov/pubmed/35887341 http://dx.doi.org/10.3390/ijms23147994 |
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