Cytology and GeneticsNov 4
Identification of Bacterial FtsZ Effectors Targeting the Sites of Coumarin Binding - #FtsZ #BP1 #BP2 #coumarins #ligandproteininteraction #chemoinformatics #pharmacophoresearch #moleculardocking #AI - https://link.springer.com/article/10.3103/S0095452725050056
Identification of Bacterial FtsZ Effectors Targeting the Sites of Coumarin Binding - Cytology and Genetics

Abstract— There is a large group of bacterial FtsZ inhibitors, the biological activity of which 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 targeting sites of 4-hydroxycoumarin binding (BP1 and BP2). New data based on original results of pharmacophore screening, chemoinformatics, molecular docking, molecular dynamics simulations, AI-predictions, etc., are presented. The object of the study was a combined library of 379 compounds, formed based on revision of the structural database RCSB Protein Data Bank and biochemically proven FtsZ effectors from ChEMBL. Based on the results of a comprehensive study, 39 compounds were selected, of which 28 were identified as effectors of the sites BP1 and BP2, and another 11 as specific effectors of the site BP2 located in the BP2/IDC superpocket.

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Cytology and GeneticsJan 30, 2025
Identification of FtsZ Interdomain Cleft Effectors Based on Pharmacophore Search and Molecular Docking - #FtsZ #IDC #effectors #ligandproteininteraction #pharmacophoresearch #moleculardocking - https://link.springer.com/article/10.3103/S0095452724050050
Identification of FtsZ Interdomain Cleft Effectors Based on Pharmacophore Search and Molecular Docking - Cytology and Genetics

Abstract 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.

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