Ab initio molecular simulations on the binding properties between mycobacterial FtsZ and its inhibitor

Filamenting temperature-sensitive mutant Z (FtsZ) is recognized to be essential for performing bacteria cell division. Since the inhibition of activity and polymerization of FtsZ prevents the mycobacteria reproduction, five types of FtsZ inhibitors were defined in the previous experiments, and their effect on FtsZ was investigated. In the present study, we employ these inhibitors as ligands and investigate the specific interactions between FtsZ and these inhibitors at atomic and electronic levels, using ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics optimization and ab initio fragment molecular orbital (FMO) calculations. From the ab initio molecular simulations, some key amino acid residues of FtsZ for the strong binding between FtsZ and ligand are highlighted. Based on the results, we propose a new inhibitor and demonstrate that it has a large binding affinity to FtsZ to be a potent inhibitor to FtsZ.