Molecular docking and molecular dynamic simulation of Curcumin on three pre-apoptotic factors of Bad, Bak, and Bim

Curcumin, a polyphenol compound, is derived from the plant Curcuma longa. This antioxidant with apoptoticeffects can lead cells to death especially in cancer cells. This molecular dynamic and molecular dockingsimulation study investigated the effects of curcumin on three pre-apoptotic factors of Bad, Bak, and Bim.The PDB files of these three factors were obtained from www.rcsb.org and the ۳D structure of curcumin wasobtained from PubChem and converted to a PDB file by Avogadro v.۱.۲ software. Via GROMACS ۲۰۱۸,studies on molecular dynamic simulation were conducted in water and ion environment. Furthermore,AutoDock v.۴.۲.۶ software performed the docking of curcumin as a ligand to these pre-apoptotic proteins.Also, LigPlot+ v.۴.۵.۳ was used to determine the hydrogen and hydrophobic bonds at the binding sites.Curcumin with the highest tendency could bind to Bad by -۶.۵۸ kcal/mol of binding energy. In addition, thebinding of curcumin to the other proteins induced some changes in molecular dynamic factors such as radiusof gyration (Rg), root-mean-square deviation (RMSD), and root-mean-square fluctuation (RMSF). Asignificant increase in Rg and RMSD was seen in Bad and Bak after docking with curcumin. Moreover,curcumin induced some variations in RMSF and secondary structure in these factors. According to this study,curcumin could bind to Bad, Bak, and Bim directly, induce conformational changes, and increase theirlikelihood of dimerization that can lead to activating apoptotic pathways. These results confirmed theapoptotic effects of curcumin on cancer cells.

کلیدواژه ها:

Bad ، Bak ، Bim ، Curcumin ، Molecular dynamics