Molecular Docking Studies of Selected Inhibitors of β-cell Lymphoma-2 Family Proteins
Keywords:Cancer, B-cell lymphoma 2 (BCL-2), Docking analysis, Binding affinity, SBDD
Thirty-six compounds obtained from the PubChem database were used to study the inhibition of BCL-2 receptor through a computational-aided drug-design technique. The molecular docking of all the ligands was evaluated for binding to BCL-2 protein (apoptosis regulator). All the selected chemical datasets were drawn with Chemdraw program and docked within the binding pocket of BCL-2 using ICM-pro molsoft software. The structures of AP7 and AP26 were modified to form new compounds designated AP7a and AP26a respectively. The binding energies of AP7a and AP26a were determined as well as those of the thirty-six lead compounds. Ligands AP7 (-25.313 kcal/mol) and AP26 (-29.430 kcal/mol) were the best of all the 36 compounds. A notable improvement was seen in the binding pose of the modified compounds where the result of the binding energy values of AP7a and AP26a was found to be -25.264 kcal/mol and -26.0851kcal/mol respectively. The number of hydrogen bonds found in AP7a was significantly more than its parent lead. These bonds were formed between the compound and the following 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: 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 aforementioned results showed that the newly designed compounds were better BCL-2 apoptosis regulator inhibitors compared with the 36 compounds used for the study, due to the significant hydrogen bond energies formed by the novel compounds.
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