Molecular Docking Studies of Selected Inhibitors of β-cell Lymphoma-2 Family Proteins

Abstract
In this study, thirty-six compounds obtained from the PubChem database were used to investigate the inhibition of the BCL-2 receptor via a computational-aided drug-design technique. The molecular docking of all the ligands was assessed for binding to the BCL-2 protein, an apoptosis regulator. The chemical datasets were drawn with Chemdraw, and then docked within the binding pocket of BCL-2 using ICM-pro molsoft software. AP7 and AP26 were then modified to form new compounds - AP7a and AP26a - respectively. The binding energies of AP7a and AP26a, along with the thirty-six lead compounds, were determined. The highest binding energies were found to be -25.313 and -29.430 kcal/mol for AP7 and AP26 respectively. A notable improvement was observed in the binding pose of the modified compounds, as the binding energy values for AP7a and AP26a were -25.264 kcal/mol and -26.0851 kcal/mol, respectively. Furthermore, the number of hydrogen bonds formed by AP7a was significantly more than that of its parent lead. These bonds were formed between the compound and the amino acids ARG139 (2.05Å), TRY180 (1.55Å), LEU59 (1.76Å), GLU135 (2.63Å) and ARG139 (1.82Å). The binding pose of AP26a was found to have seven hydrogen bonds, with HIS120 (2.13Å), ARG129 (1.72Å), Leu59 (1.98 Å), SER60 (2.64 Å), LYS58 (2.63), GLN118 (1.95 Å) and THR132 (2.54Å). The results of this study showed that the newly designed compounds had greater potential as BCL-2 apoptosis regulator inhibitors compared to the 36 compounds used, due to the formation of significant hydrogen bond energies by the novel compounds.

https://www.nsbmb.org.ng/journals/index.php/njbmb/article/view/155