Exploration of the binding of benzimidazole-biphenyl derivatives to hemoglobin using docking and molecular dynamics simulation

Abstract

In this study, the binding of hemoglobin (Hb) with three benzimidazole-biphenyl derivatives (telmisartan (TST), candesartan (CST), and DB921) is investigated by molecular docking, molecular dynamics (MD) simulation, and binding free energy calculation. Results demonstrate that the three drugs locate in the cavities formed by α 1, α 2, and β 2 subunits. The average gyration radii are estimated and consistent with available experimental results. The binding free energies suggest that the binding site of CST/Hb is more stable than those of TST/Hb and DB921/Hb. The energy decomposition analysis is performed and reveals that the electrostatic interactions play an important role in the stabilization of the binding site of CST/Hb or DB921/Hb while the van der Waals interactions contribute largely to stabilization of the binding site of TST/Hb. The key residues stabilizing the binding sites of TST/Hb, CST/Hb, and DB921/Hb are identified based on the residue decomposition analysis. The probability densities of salt bridge distances demonstrate that there still exist the four salt bridges between α 1 and α 2 subunits of Hb in presence of these drugs.