Identification of FtsZ Interdomain Cleft Effectors Based on Pharmacophore Search and Molecular Docking

There are a significant number of inhibitors of the bacterial FtsZ protein with biochemically confirmed biological activity, at the same time, their binding sites remain unclear. This significantly complicates further combinatorial design, and, in the current study, the results of a computational search for effectors of the Inter-Domain Cleft (IDC) site are presented. The actual research was based on the results of pharmacophore screening using the Pharmit service and molecular docking with CCDC GOLD and iGEMDOCK programs. The objective group was a combined library of 379 compounds, which was designed based on revision of the structural database of the RCSB Protein Data Bank and compounds from the ChEMBL database, for which direct interaction with FtsZ has been proven biochemically. According to the results of pharmacophore search, docking, and structural analysis, 88 effectors of the IDC site were identified. One more curcumin compound has been identified as a potential IDC site effector.