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.