Binding sites of Zantrin inhibitors to the bacterial cell division protein FtsZ: molecular docking and ab initio molecular orbital calculations

Abstract Filamentous temperature-sensitive Z (FtsZ) protein contributes to bacteria cell division, and its inhibition prevents Mycobacteria reproduction. In the present study, Zantrin Z3 and ZZ3 were adopted as inhibitors against FtsZ and their binding properties to FtsZ were investigated, using ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics and ab initio fragment molecular orbital (FMO) calculations. From the total energies of several structures evaluated by the ab initio FMO calculations, we specified the most preferable binding-sites of Z3/ZZ3 to FtsZ and highlighted the key amino acid residues contributing to the binding of these inhibitors at an electronic level. In addition, we revealed the reason why ZZ3 is more potent against FtsZ than Z3 and that ZZ3 is effective for inhibiting the FtsZ aggregation.