The effect of metformin on Bad, Bak, and Bim pro-apoptotic factors: A molecular dynamic simulation study

Abstract

Recent investigations have demonstrated that metformin treatment can decrease tumor incidence and growth using cell cycle arrest and induction of apoptosis pathway. However, it is not clear how metformin affects the factors involved in the apoptotic process. The present study aimed to determine the effect of metformin on Bak, Bad, and Bim pro-apoptotic proteins using docking and dynamics simulation studies. The 3D structure of molecules was retrieved from PubChem and RCSB servers. Simulation and docking studies were conducted by Gromacs and AutoDock software. Next, molecular dynamics analysis was performed using Gromacs software. Moreover, LigPlot+V.4.5.3 software was applied for the determination of the hydrogen and hydrophobic interactions at the binding sites. Our findings demonstrated that metformin has the highest affinity for binding the Bak protein. This binding occurred using four amino acid residues within the binding site of Bak with the minimum binding energy (-5.70 kcal/mol). The molecular docking of metformin to these pro-apoptotic factors significantly decreased the total energy and increased the coil secondary structure of Bak protein. According to our findings, metformin can alter the molecular dynamics property of these proteins which results in increased activity of these pro-apoptotic proteins and induction of apoptosis.