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

Author(s)

Povinelli, Ana Paula Ribeiro ; Zazeri, Gabriel ; Jones, Alan M. ; Cornelio, Marinonio Lopes

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 14, p. 14-pg., 2022-07-01.

Abstract

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-kappa B 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 alpha-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. (AU)

• FAPESP's process: 17/08834-9 - Experimental and computational assays on molecular targets with pharmacological importance and interactions with natural products
• Grantee: Marinônio Lopes Cornélio
• Support Opportunities: Regular Research Grants