Fig. 5: Molecular docking to identify unique residues of (A) Gyrase and (B) Topoisomerase IV involved in key interactions with BWC0977.

The crystal bound conformations of ciprofloxacin mapped to EcGyrase (A), and EcTopoIV (B). The residues which form key ion-mediated interactions are shown as sticks and labelled. Mg²⁺ ions are shown as black spheres and ion-mediated interactions are highlighted with broken lines. The BWC0977 binding orientation determined by molecular docking is also shown as sticks to illustrate the variable binding pockets. All key interaction residues of BWC0977 are minimum 4 atoms away from the ciprofloxacin ligand atoms. Also, the DNA bases where BWC0977 left-hand side (LHS) ring stack are different from ciprofloxacin interacting DNA base pairs. Therefore, none of the BWC0977 interacting amino acid residues are directly involved in ciprofloxacin binding, implicating an unlikely possibility of development of cross-resistance.