A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction
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Data
2022-07-01
Autores
Povinelli, Ana Paula Ribeiro
Zazeri, Gabriel
Jones, Alan M.
Cornélio, Marinônio Lopes [UNESP]
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Resumo
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.
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fluorescence spectroscopy, IL6, Interleukin-6, molecular biophysics, molecular docking, piperine, umbrella sampling
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International Journal of Molecular Sciences, v. 23, n. 14, 2022.