Computational Insights into the Interaction of Pinostrobin with Bcl-2 Family Proteins: A Molecular Docking Analysis

Abstract

Background: Cancer research has emphasized the Bcl-2 family of proteins because of their interaction in apoptosis process, a critical mechanism that regulates cellular survival and death. Recently small molecules from diverse sources have gained much attention in anticancer research due to their promising inhibitory action against Bcl-2 and Bcl-XL that are pointedly known as the members of anti-apoptotic Bcl-2 family of proteins. Pinostrobin (PN) is a natural flavonoid with diverse pharmacological potential emerged as a molecule of interest as anticancer agent. The present study aims to screen the interaction of PN with anti-apoptotic protagonists Bcl-2 and Bcl- XL at the molecular level through docking studies. Method: The molecular docking was performed using the Schrodinger software. The docking score of PN with the Bcl-2 (4IEH) and Bcl-XL (3ZK6) and their molecular interactions was examined and analysed. Results: The result of the molecular docking analysis showed that PN and the anti-apoptotic proteins 4IEH and 3ZK6 had significant interactions and docking energy scores (ΔG) were found to be -5.112 kcal/mol and -7.822 kcal/mol respectively. The small molecule PN illustrated effective interaction with the active site amino acids of the Bcl-2 and Bcl-XL proteins and has been associated through traditional hydrogen bond with 4IEH. Further, it was observed that PN and anti-apoptotic Bcl-2 proteins interaction was stabilized by other non-covalent interactions, such as π-alkyl or π-π interactions and van der Waals forces.Conclusions: This was the first study to reveal the inhibitory action of PN against anti-apoptotic Bcl-2 and Bcl-XL proteins at the molecular level. The findings of this study concludes that PN ability to inhibit anti-apoptotic proteins, Bcl-2 and Bcl-XL could be useful to induce intracellular apoptosis in tumorous cells.