Mastodawn

Identification of FtsZ Protein Nucleotide-Binding Site Effectors Based on Cheminformatics and Structural-Biological Analysis - #FtsZ #nucleotidebindingsite #interdomaincleft #effectors #ligand–proteininteraction #FragFp #pharmacophoresearch #moleculardocking #artificialintelligence #cheminformatics #structuralbiologicalanalysis - https://link.springer.com/article/10.3103/S0095452725040073

Identification of FtsZ Protein Nucleotide-Binding Site Effectors Based on Cheminformatics and Structural-Biological Analysis - Cytology and Genetics

There is a large group of bacterial FtsZ inhibitors whose biological activity has been confirmed biochemically. However, the sites of protein–ligand interaction for most of them remain unknown, significantly complicating the further search and combinatorial design of FtsZ inhibitors. This study presents the results of bioinformatic analysis of bacterial FtsZ effectors, the interaction of which has been proven and documented in the ChEMBL database of biologically active molecules. With an integrated approach based on chemo- and bioinformatic methods and AI-based predictions, 23 inhibitors of nucleotide-binding site (NBS), as well as 16 new effectors of the interdomain cleft (IDC), were identified.

SpringerLink

Cytology and Genetics Dec 18, 2024

Ligand-Induced Variability of the FtsZ Protein Interdomain Site Pocket - #FtsZ #interdomaincleft #IDCsite #conformationalvariability #inhibitors - https://link.springer.com/article/10.3103/S0095452724040078

Ligand-Induced Variability of the FtsZ Protein Interdomain Site Pocket - Cytology and Genetics

Abstract 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.

SpringerLink