Homology Modeling and Docking Studies of a Cell Division Protein, FtsZ: Taxanes and Flavonoids as Anti-FtsZ Agents

In Enterococcus faecalis and other bacteria, FtsZ is an essential cell division protein. The three dimensional structure of FtsZ from E. faecalis was built by four online servers: SWISS-MODEL, RaptorX, CPHmodels-3.0 and IntFOLD. Evaluation of the models was performed by ERRAT, QMEAN6, DFIRE, PROCHECK and MolProbity server. SWISS- MODEL produced the best quality model in ERRAT and the best Ramachandran plot values in PROCHECK and selected for docking experiment. An active site for GTPase was predicted which consists mainly of the amino acid residues: 21-23, 72-74, 105-111, 136,140,144,167 and 187. Docking of hundred compounds using Hex 8.0.0 against FtsZ of E. feacalis, Staphylococcus aureus, S. epidermidis, Bacillus subtilis, and Pseudomonas aeruginosa was carried out in order to find FtsZ inhibitors. Taxanes and hinokiflavone had the best binding energy values. Other flavonoids i.e. rutin, vicenin, scutellarin, amentoflavin, silybin and the polyphenolic curcumin also had docking results better than GTP which was used as control. The results concluded that these flavonoids could be used as anti-FtsZ compounds and may replace the cytotoxic taxanes as new antimicrobial agents directed against this potential target.