In Silico Study of the Effect of Thymoquinone on Three Pre-apoptotic Factors of Bad, Bak, and Bim

Abstract

Background: Apoptosis is one of the most vital mechanisms in the removal of old and damaged cells, especially cancer cells. Many polyphenolic and antioxidant compounds can inhibit the growth and proliferation of cancer cells by inducing apoptosis. This study intended to evaluate the effect of the thymoquinone (TQ) on the three pre-apoptotic factors Bad, Bak, and Bim in the simulation environment. Methods: The Protein Data Bank (PDB) files of three pre-apoptotic proteins Bad, Bak, and Bim were obtained from PDB database and the molecular structure of TQ from PubChem database. The optimization, simulation, molecular docking, and molecular dynamics (MD) computation were performed using AutoDock, VMD, and GROMACS packages on each one of the proteins in free mode and ligand binding mode. Results: The number and type of hydrogen and hydrophobic bonds at the binding site of TQ and pre-apoptotic factors Bad, Bak, and Bim were detected at the lowest level of energy. The lowest binding energy level of TQ had the highest tendency to bind to the BAD molecule. After the binding of TQ to proteins, the radius of gyration (Rg) of Bim increased while the Rg of Bad and Bak decreased. However, the secondary structures (Turn, Coil, Helix, and Bend) were greatly affected in the binding of TQ to Bad, Bak, and Bim. Conclusion: The variations of binding energy indicated that TQ can affect the three pre-apoptotic factors Bad, Bak, and Bim. This bond seems to increase their activity by variation in the secondary structure of the Bim specific residues.