Computational ligand–receptor docking simulation of piperine with apoptosis-associated factors

Abstract

Although widely known for its antioxidant properties, piperine's (a compound from the pepper plant) physiologic involvement in apoptosis (programmed cell death) is unclear. As a prerequisite to unravel its role in this process, computational approaches simulating ligand-receptor docking are sought. Herein, we report the simulated binding of piperine with major apoptotic proteins via combined deployment of AutoDock suite (AutoDock Vina), PyMOL, and LigPlot + software. Our results demonstrated varied binding affinity toward the different apoptosis-associated proteins with a higher to lower affinity pattern in the order of TNFR-1 > Caspase-3 > TNF-α > Caspase-8 > Bcl-2 > Caspase-9 > Bax. Docking scores for all receptor-ligand interactions indicate a strong likelihood of impromptu receptor-ligand binding. Molecularly, the simulated analysis revealed hydrophobic interactions in all receptor-ligand models studied. Receptor-piperine complexes involving TNFR-1 and Caspase-8 showed single hydrogen bonding whereas amino acid residues of TNF-α exhibited double hydrogen bonding to piperine. In the TNFR-1-piperine complex (receptor-ligand docked model with strongest binding affinity) the hydrophobic interaction involves amino acid residues of SER74, LYS75, ASN110 (2), THR94, CYS96, VAL95, and PHE112. Our findings provide novel in silico evidence of piperine's binding affinity toward apoptosis-associated proteins and the high likelihood of its influence on apoptosis reaction via the extrinsic pathway.

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“…To begin the docking analysis, a set of codes (commands) was written in the command prompt to generate the output score. 43 The results displayed the values of binding energy or the Gibbs free energy ( G ) in kcal mol −1 , and the ligand with the maximum negative value was considered to have the highest binding affinity for a particular target protein. The results displayed the values of binding affinity and Gibbs free energy ( G ) in kcal mol −1 , and the ligand with the maximum negative value was considered to have the highest binding affinity for a particular target protein.…”