The Cytokine IL-1β and Piperine Complex Surveyed by Experimental and Computational Molecular Biophysics.
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-1β). However, investigation into the molecular interactions between IL-1β and piperine is not reported in the literature. Here, we present for the first time the characterisation of the complex formed by IL-1β 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 × 104 M-1 at 298 K. The thermodynamic analysis indicated that the interaction with IL-1β was spontaneous (∆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-1β secondary structure (~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-1β, corroborating the circular dichroism data.
['Zazeri|Gabriel|G|0000-0001-9957-9697', 'Povinelli|Ana Paula Ribeiro|APR|0000-0001-6282-5380', 'de Freitas Lima|Marcelo|M|0000-0003-3191-2494', 'Cornélio|Marinônio Lopes|ML|0000-0002-0755-8643']
D000465:Algorithms D000470:Alkaloids D052117:Benzodioxoles D001665:Binding Sites D055592:Biophysical Phenomena D002942:Circular Dichroism D053583:Interleukin-1beta D007700:Kinetics D008956:Models, Chemical D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D010880:Piperidines D053284:Polyunsaturated Alkamides D011485:Protein Binding D011487:Protein Conformation D013050:Spectrometry, Fluorescence D013816:Thermodynamics
cytokine IL-1β piperine fluorescence spectroscopy molecular docking umbrella sampling