Ligand-Induced Variability of the FtsZ Protein Interdomain Site Pocket

The variability of the allosteric binding site pocket located in the interdomain cleft (IDC) of FtsZ proteins was investigated. The point-cloud models of the IDC site pockets were constructed based on 11 structures for the S. aureus complexes of FtsZ protein with 2,6-diflurobenzamides—OLQ, 9PC, OM8, OMW ZI1, ZI6, ZI7, and ZI9—which is currently deposed in the RCSB Protein Data Bank. Significant variability in the volume and shape of the IDC site pocket, formed under adaptation to the ligand, was demonstrated. Four main conformational states of the site pocket, resulting from ligand-protein fitting were selected. It indicates that the docking of the ligands into the IDC site of individual 3D-models of FtsZ protein molecules is not effective. It was concluded that virtual screening efficiency can be significantly improved by the use of an ensemble of molecular targets considering the conformational variability of the IDC site pocket of bacterial FtsZ protein.