20.500.12556/RUL-182641 In silico druggability assessment of Escherichia coli FtsQ reveals tractable PPI interfaces in the divisome Background/Objectives: Due to the widespread problem of antimicrobial resistance (AMR), there is an urgent need to identify new antibacterial targets that act through mechanisms distinct from those of existing antibiotics. One of these targets is the essential cell division protein FtsQ, which is a central hub of the Gram-negative divisome, but the druggability of its extensive protein–protein interaction (PPI) interfaces remains poorly defined. Here, we present a comprehensive structure-based in silico characterization of Escherichia coli FtsQ aimed at identifying and prioritizing druggable regions for PPI modulation. Methods: We analyzed E. coli FtsQ in both apo and complexed states (FtsQB, FtsQL, and FtsQBL) using a combination of pocket-mapping tools (FTMap and SiteMap), evolutionary conservation analysis (ConSurf), and structure property assessment (BLAST, ProBiS) to map and evaluate potential binding pockets of FtsQ protein. Results: Eight potential binding sites were predicted across the β and POTRA domains of FtsQ. One previously unreported site within the POTRA domain was prioritized as a candidate site, characterized by favorable druggability scores, strong evolutionary conservation, and a putative role in the FtsQ–FtsW/FtsN/FtsI interaction network. In contrast, two highly conserved sites at the FtsQ–FtsB/FtsL interaction interface were structurally flat, indicating limited suitability for classical small-molecule binding and greater compatibility with alternative modalities such as macrocycles or peptidomimetics. Conclusions: Although FtsQ lacks deep canonical binding pockets, this study proposes several conserved and potentially tractable regions as candidate sites, supporting its potential as a non-classical but promising antibacterial target for disrupting bacterial cytokinesis. antimicrobial resistance gram-negative bacteria FtsQ bacterial cell division divisome protein–protein interactions druggability assessment structure-based drug design in silico analysis pocket mapping POTRA domain antibacterial targets interakcije beljakovine-beljakovine ocena zdravilne sposobnosti načrtovanje zdravil na podlagi strukture in silico analiza kartiranje žepov domena POTRA antibakterijske tarče bakterijska rezistenca tarčna zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2026-05-20 07:57:51 2026-05-20 07:58:00 2026-05-21 04:57:09 0000-00-00 00:00:00 2026 0 0 29 str. iss. 5, art. 430 Vol. 15 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.015.8+615.2-021.321 2079-6382 10.3390/antibiotics15050430 277083139 antibiotics-15-00430-v2.pdf antibiotics-15-00430-v2.pdf 1 D887AD298079C70A470E02C65F54754E c23c33491c865430b2c565a5dda145dce218ef329faceac0e83896b4bb15ab8d e9515f9a-5410-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234089 https://www.mdpi.com/2079-6382/15/5/430 1 8a86a6b7-5410-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234088 Fakulteta za farmacijo 0 0 0