Evaluation Of Curcumin Effects On Bad, Bak, And Bim: A Molecular Dynamics Simulation Study

Curcumin (Cur) is a polyphenol compound with antioxidant and apoptotic effects. It can lead cells to death which is the ultimate goal in cancer research. The effect of Cur on three pro-apoptotic factors of Bad, Bak, and Bim was investigated in this molecular dynamic and molecular docking simulation study. The PDB files of these three factors and the 3-D structure of Cur were obtained from www.rcsb.org and PubChem, respectively. All files were converted to PDB files by Avogadro v.1.2 software. The water and ion environment in GROMACS 2018 simulation package was used to conduct molecular dynamic simulation studies. Furthennore,AutoDock v.4.2.6 software performed the docking of Cur as a ligand and the proteins as receptors. LigPlot+ v.4.5.3 was used to determine the hydrogen and hydrophobic bonds at the binding sites. Results showed that Cur could bind to Bad with -6.58 kcal/mol binding energy. In addition, the binding of Cur to proteins induced some changes in molecular dynamic factors such as radius of gyration (Rg), root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), binding energy (BE), estimated inhibition constant (EIC), and their secondary structures. A significant increase in Rg and RMSD and some variations in RMSF were seen in Bad and I3ak after docking with Cur. Considering this study, Cur could bind to the proteins directly, induce conformational changes, and increase their likelihood of dimerization, leading to activating apoptotic pathways. These results suggested the apoptotic effects of Cur on cancer cells through influencing these proteins for the first time.