3.2 Computational molecular docking determining the interaction
between HCQ, AZM and hERG
The above findings, particularly those concerning pharmacological
effects on hERG, prompted computational molecular docking explorations
for possible interactions between HCQ and AZM and a recent hERG
homotetramer structure (PDB ID: 5va2). Fig.4 illustrates HCQ-hERG and
AZM-hERG interactions derived from molecular docking. HCQ interacts
predominantly with Y652 and F656 from one or more subunits (Fig.4B-D).
The Induced Fit Docking (IFD) protocol enabled HCQ to enter the space
between the S5 and S6 helices. Other hERG residues involved in
interactions with HCQ included F557, L622, T623, S624, and S660. Docking
of AZM (Figure 4E-F) indicated similar, albeit less frequent
interactions. This was reflected in an approximately two-fold weaker IFD
score for AZM than for HCQ (-922 and -18340 for top-scoring positions,
respectively). Variability in observed docking positions of ligands
could be attributed to the highly symmetric structure of the hERG
channel pore enabling many equivalent positions.