The Cytokine IL-1 beta and Piperine Complex Surveyed by Experimental and Computational Molecular Biophysics

Author(s)

Zazeri, Gabriel ^[1] ; Ribeiro Povinelli, Ana Paula ^[1] ; Lima, Marcelo de Freitas ^[2] ; Cornelio, Marinonio Lopes ^[1]

Affiliation

^[1] UNESP, Dept Fis, Inst Biociencias Letras & Ciencias Exatas IBILCE, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto - Brazil

^[2] UNESP, Dept Quim, Inst Biociencias Letras & Ciencias Exatas IBILCE, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto - Brazil

• Document type: Journal article
• Source: BIOMOLECULES; v. 10, n. 9 SEP 2020.
• Web of Science Citations: 2

Abstract

The bioactive piperine, a compound found in some pepper species, has been widely studied because of its therapeutic properties that include the inhibition of an important inflammation pathway triggered by interleukin-1 beta (IL-1 beta). However, investigation into the molecular interactions between IL-1 beta and piperine is not reported in the literature. Here, we present for the first time the characterisation of the complex formed by IL-1 beta and piperine through experimental and computational molecular biophysical analyses. Fluorescence spectroscopy unveiled the presence of one binding site for piperine with an affinity constant of 14.3 x 10(4) M-1 at 298 K. The thermodynamic analysis indicated that the interaction with IL-1 beta was spontaneous Delta G = -25 kJ/mol) and, when split into enthalpic and entropic contributions, the latter was more significant. Circular dichroism spectroscopy showed that piperine did not affect IL-1 beta secondary structure (similar to 2%) and therefore its stability. The set of experimental data parameterized the computational biophysical approach. Through molecular docking, the binding site micro-environment was revealed to be composed mostly by non-polar amino acids. Furthermore, molecular dynamics, along with umbrella sampling, are in agreement with the thermodynamic parameters obtained by fluorescence assays and showed that large protein movements are not present in IL-1 beta, corroborating the circular dichroism data. (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