Molecular dynamics simulation study of the effect of hesperetin on pre-apoptotic factors of Bad, Bak, and Bim

Abstract

Background and Aim: Many compounds derived from medicinal plants, such as antioxidants and polyphenols have significant roles in prevention and treatment of various cancers. Activation of apoptosis related pathways is one of the mechanisms for inhibition of cancer progression. In this study, we investigated the effect of molecular dynamics simulation of hesperetin on the pre-apoptotic factors of Bad, Bak, and Bim. Material and Methods: In this study we collected data about 3 dimensional structure and Protein Data Bank (PDB) files of three apoptotic factors of Bad, Bak, and Bim from Protein Data Bank (http://www.rscb.org/pdb). Using VMD v1.9.2, AutoDock v.4.2, and Gromacs v.4.5.4 softwares, we started processes such as optimization, simulation, molecular docking and molecular dynamics calculations. Results: Binding of Bad molecule to hesperetin led to release of the highest amount of energy and reduced changes in the radius of gyration of Bad protein. But after binding of Bim and Bak proteins to hesperetin, changes in the radius of gyration, increased. The most frequent change in the secondary protein structure was related to increased amount of Bent structure and decreased amount of β-sheet structure in Bim molecule. Conclusion: Hesperetin can affect the activities of pre-apoptotic factors of Bad, Bak, and Bim by influencing their molecular dynamics. It seems that hesperetin has the highest effect on the activation of Bad molecule. Also, it can activate Bim protein and induce apoptosis via inducing alternations in the secondary structure of the protein.

Keywords

• molecular dynamics
• apoptosis
• hesperetin