همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

AcrB Inhibition: A Molecular Docking Approach to Combat Escherichia coli Infections

نویسندگان :

Faezeh Mohammadzadeh Habil¹ ٍElnaz Afshari²

1- دانشگاه آزاد اسلامی واحد تهران مرکزی 2- دانشگاه شهید بهشتی

کلمات کلیدی :

Escherichia coli،AcrB protein،Molecular Docking

چکیده :

Introduction Urinary tract infections caused by multi-drug resistant Escherichia coli pathogens continue to pose significant challenges in clinical treatment (Chauhan et al., 2024). One of the primary mechanisms by which E. coli acquire antibiotic resistance is through efflux pumps, the AcrB system, which actively transport antibiotics from within bacterial cells to the external environment. A promising strategy for enhancing antibiotic efficacy and the effects of treatments involves the development of effective derivatives that can inhibit these pumps, potentially overcoming E. coli resistance (Chauhan et al., 2024). Therefore, in this study, we aimed to determine the most potent inhibitor of AcrB through molecular docking analysis. Material and Methods For this purpose, the three-dimensional structure of the AcrB protein (PDB ID: 2dhh) was obtained from the RCSB PDB database. Three AcrB inhibitory ligands (with PubChem CID: 13806, 222528, and 2993) and 10 analogs for each ligand were retrieved from the PubChem databases. The protein and inhibitory ligands were prepared for docking using Molegro Virtual Docker version 6.0. After docking, the best interaction with the lowest energy binding was analyzed through Molegro Molecular Viewer v.7 software. Finally, the pharmacokinetic properties of the ligand were evaluated using the SwissADME server. Results and Conclusion Through all inhibitory ligands for AcrB protein, the best ligand was 2-[3,6-bis(dimethylamino)-2,7-diphenylxanthen-10-ium-9-yl]benzoic acid (Pumchem CID: 101886889) with a molecular weight of 539.64 g/mol and binding energy of -132.82 kcal/mol. This ligand created seven steric interactions with the AcrB protein residues of Gly97(A), Ala100(A), Asp101(A), Gln106(B), Thr98(B), Asp99(B), and Asp99(A), one hydrogen bond with Asp99(A) residue, and two electrostatic interactions with Asp99(A) and Asp101(A). In addition, the ADME results demonstrated that this ligand has a water solubility score (logS) of -7.37, a hydrophilic score (LogP) of 1.64, a polarity score (TPSA) of 56.92 A, and lastly, hydrogen bond donors of 1 and hydrogen bond acceptors of 3. These results indicated that 2-[3,6-bis(dimethylamino)-2,7-diphenylxanthen-10-ium-9-yl]benzoic acid (Pumchem CID: 101886889) is a promising candidate for inhibiting Escherichia coli resistance, although further in vitro and in vivo studies are required to confirm its potential as therapeutic agents.