Molecular docking and dynamic simulation of anti-apoptotic BCL-2 with saponins isolated from Weigela x “Bristol Ruby”

Abstract

Colon cancer is the second leading cause of cancer-related deaths worldwide. Apoptosis may play a key role in the tissue mass homeostasis of the colonic mucosa. The B-cell lymphoma-2 (BCL-2) family plays an important role in determining the decision to undergo apoptosis. A previous study revealed the potential cytotoxicity on colorectal cancer cell line of triterpenoid saponins isolated from Weigela x “Bristol Ruby”. In this in silico study, triterpenoid saponins from W. x “Bristol Ruby” were studied for their inhibition potential using molecular docking on the 6GL8 receptor. All compounds exhibited hydrogen bonds, Van der Waals, and hydrophobic interactions in molecular docking. The binding potentials of triterpenoid saponins and a reference compound, 5-FU, as target protein 6GL8 were examined using molecular docking. Among of those, 3-O-β-D-xylopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid (CPD1) binds to the 6GL8 receptor with the highest binding stabilities as -5.08 kcal/mol, in comparison with the reference 5-FU as -3.59 kcal/mol. Molecular dynamic studies were further conducted to better comprehend ligands’ dynamics within the target protein’s binding pocket. The result showed that the binding of CPD1 to the 6GL8 receptor was stable throughout the simulation. CPD1 could be a good candidate for new inhibitors of anti-apoptotic BCL-2 proteins in colorectal cancer.