{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:34:54Z","timestamp":1776209694616,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> This work utilizes predictive modeling in drug discovery to unravel potential candidate genes from <jats:italic>Escherichia coli<\/jats:italic> that are implicated in antimicrobial resistance; we subsequently target the gidB, MacB, and KatG genes with some compounds from plants with reported antibacterial potentials.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> The resistance genes and plasmids were identified from 10 whole-genome sequence datasets of <jats:italic>E. coli<\/jats:italic>; forty two plant compounds were selected, and their 3D structures were retrieved and optimized for docking. The 3D crystal structures of KatG, MacB, and gidB were retrieved and prepared for molecular docking, molecular dynamics simulations, and ADMET profiling.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> Hesperidin showed the least binding energy (kcal\/mol) against KatG (\u22129.3), MacB (\u221210.7), and gidB (\u22126.7); additionally, good pharmacokinetic profiles and structure\u2013dynamics integrity with their respective protein complexes were observed.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Although these findings suggest hesperidin as a potential inhibitor against MacB, gidB, and KatG in <jats:italic>E. coli<\/jats:italic>, further validations through <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments are needed. This research is expected to provide an alternative avenue for addressing existing antimicrobial resistances associated with <jats:italic>E. coli<\/jats:italic>\u2019s MacB, gidB, and KatG.<\/jats:p>","DOI":"10.3389\/fbinf.2024.1411935","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:34:11Z","timestamp":1721968451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes from E. coli whole-genome sequences"],"prefix":"10.3389","volume":"4","author":[{"given":"Abdullahi Tunde","family":"Aborode","sequence":"first","affiliation":[]},{"given":"Neeraj","family":"Kumar","sequence":"additional","affiliation":[]},{"given":"Christopher Busayo","family":"Olowosoke","sequence":"additional","affiliation":[]},{"given":"Tope Abraham","family":"Ibisanmi","sequence":"additional","affiliation":[]},{"given":"Islamiyyah","family":"Ayoade","sequence":"additional","affiliation":[]},{"given":"Haruna Isiyaku","family":"Umar","sequence":"additional","affiliation":[]},{"given":"Abdullahi Temitope","family":"Jamiu","sequence":"additional","affiliation":[]},{"given":"Basit","family":"Bolarinwa","sequence":"additional","affiliation":[]},{"given":"Zainab","family":"Olapade","sequence":"additional","affiliation":[]},{"given":"Abidemi Ruth","family":"Idowu","sequence":"additional","affiliation":[]},{"given":"Ibrahim O.","family":"Adelakun","sequence":"additional","affiliation":[]},{"given":"Isreal Ayobami","family":"Onifade","sequence":"additional","affiliation":[]},{"given":"Benjamin","family":"Akangbe","sequence":"additional","affiliation":[]},{"given":"Modesta","family":"Abacheng","sequence":"additional","affiliation":[]},{"given":"Odion O.","family":"Ikhimiukor","sequence":"additional","affiliation":[]},{"given":"Aeshah A.","family":"Awaji","sequence":"additional","affiliation":[]},{"given":"Ridwan Olamilekan","family":"Adesola","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.1007\/s00210-023-02551-0","article-title":"The anti-tumoral role of Hesperidin and Aprepitant on prostate cancer cells through redox modifications","volume":"396","author":"Akbari","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Archives Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"791","DOI":"10.3390\/gels9100791","article-title":"Formulation and characterization of hesperidin-loaded transethosomal gel for dermal delivery to enhance antibacterial activity: comprehension of in vitro, ex vivo, and dermatokinetic analysis","volume":"9","author":"Alam","year":"2023","journal-title":"Gels"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.3390\/cimb45020093","article-title":"Synthesis, molecular docking, and dynamic simulation targeting main protease (Mpro) of new, thiazole clubbed pyridine scaffolds as potential COVID-19 inhibitors","volume":"45","author":"Alghamdi","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1173624","DOI":"10.3389\/fchem.2023.1173624","article-title":"Predicting the effects of rare genetic variants on oncogenic signaling pathways: a computational analysis of HRAS protein function","volume":"11","author":"Ali","year":"2023","journal-title":"Front. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1080\/10942912.2023.2236327","article-title":"Hesperidin plays beneficial roles in disorders associated with the central nervous system: a review","volume":"26","author":"Atoki","year":"2023","journal-title":"Int. J. Food Prop."},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.22034\/mnba.2023.394932.1030","article-title":"Novel formulations of hesperidin for antitumor, antimicrobial, and neuroprotective effects: a review","volume":"2","author":"Bahador","year":"2023","journal-title":"Micro Nano Bio Asp."},{"key":"B7","doi-asserted-by":"publisher","first-page":"6073","DOI":"10.3390\/ijms23116073","article-title":"Allosteric binding sites of A\u03b2 peptides on the acetylcholine synthesizing enzyme ChAT as deduced by in silico molecular modeling","volume":"23","author":"Baidya","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1093\/bioinformatics\/btr168","article-title":"ProDy: protein dynamics inferred from theory and experiments","volume":"27","author":"Bakan","year":"2011","journal-title":"Bioinformatics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1093\/jac\/dkaa345","article-title":"ResFinder 4.0 for predictions of phenotypes from genotypes","volume":"75","author":"Bortolaia","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"B10","doi-asserted-by":"publisher","first-page":"8365","DOI":"10.1038\/srep08365","article-title":"RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes","volume":"5","author":"Brettin","year":"2015","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ijmm.2013.02.001","article-title":"Plasmids and the spread of resistance","volume":"303","author":"Carattoli","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/qua.25678","article-title":"Computational chemistry in drug lead discovery and design","volume":"119","author":"Cavasotto","year":"2019","journal-title":"Int. J. Quantum Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.3390\/biom12121871","article-title":"Plant-derived bioactive compounds and potential health benefits: involvement of the gut microbiota and its metabolic activity","volume":"12","author":"Chen","year":"2022","journal-title":"Biomolecules"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1021\/ci300367a","article-title":"admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties","volume":"52","author":"Cheng","year":"2012","journal-title":"J. Chem. Inf. Model"},{"key":"B16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-molecule library screening by docking with PyRx","volume":"1263","author":"Dallakyan","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s11030-023-10689-5","article-title":"You must be flexible enough to be trained, Mr. Dynamics simulator","author":"Danazumi","year":"2023","journal-title":"Mol. Divers."},{"key":"B18","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3390\/plants12040762","article-title":"The enhanced affinity of WRKY reinforces drought tolerance in Solanum lycopersicum L.: an innovative bioinformatics study","volume":"12","author":"Debnath","year":"2023","journal-title":"Plants"},{"key":"B19","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/1471-2164-13-256","article-title":"Impact of homologous and non-homologous recombination in the genomic evolution of Escherichia coli","volume":"13","author":"Didelot","year":"2012","journal-title":"BMC Genomics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnut.2021.688843","article-title":"Plant extracts rich in polyphenols as potent modulators in the growth of probiotic and pathogenic intestinal microorganisms","volume":"8","author":"Dimitrijevi","year":"2021","journal-title":"Front. Nutr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e75720","DOI":"10.7554\/eLife.75720","article-title":"The inherent flexibility of receptor binding domains in SARS-CoV-2 spike protein","volume":"11","author":"Dokainish","year":"2022","journal-title":"ELife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e71911","DOI":"10.7554\/eLife.71911","article-title":"An empirical energy landscape reveals mechanism of proteasome in polypeptide translocation","volume":"11","author":"Fang","year":"2022","journal-title":"ELife"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2014.00684","article-title":"Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development","volume":"5","author":"Felipe","year":"2014","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3976","DOI":"10.1080\/07391102.2018.1532818","article-title":"Novel insights into the dynamics behavior of glucagon-like peptide-1 receptor with its small molecule agonists","volume":"37","author":"Girdhar","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B25","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/pro.3923","article-title":"The Bio3D packages for structural bioinformatics","volume":"30","author":"Grant","year":"2021","journal-title":"Protein Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/(sici)1096-987x(199604)17:5\/6<490::aid-jcc1>3.0.co;2-p","article-title":"Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94","volume":"17","author":"Halgren","year":"1996","journal-title":"J. Comput. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10930-023-10113-9","article-title":"A Retrospective on the development of methods for the analysis of protein conformational ensembles","volume":"42","author":"Hayward","year":"2023","journal-title":"Protein J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","article-title":"Molecular dynamics simulation for all","volume":"99","author":"Hollingsworth","year":"2018","journal-title":"Neuron"},{"key":"B29","doi-asserted-by":"publisher","first-page":"937","DOI":"10.3390\/life13040937","article-title":"Current update on role of hesperidin in inflammatory lung diseases: chemistry, pharmacology, and drug delivery approaches","volume":"13","author":"Hosawi","year":"2023","journal-title":"Life"},{"key":"B30","doi-asserted-by":"publisher","first-page":"108369","DOI":"10.1016\/j.reprotox.2023.108369","article-title":"Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress","volume":"118","author":"Ileriturk","year":"2023","journal-title":"Reprod. Toxicol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"107322","DOI":"10.1016\/j.compbiolchem.2020.107322","article-title":"Geo-Measures: a PyMOL plugin for protein structure ensembles analysis","volume":"87","author":"Kagami","year":"2020","journal-title":"Comput. Biol. Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/msb.2013.57","article-title":"Bacterial evolution of antibiotic hypersensitivity","volume":"9","author":"L\u00e1z\u00e1r","year":"2013","journal-title":"Mol. Syst. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera-A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1021\/acsomega.8b03052","article-title":"Structural modeling and in silico screening of potential small-molecule allosteric agonists of a glucagon-like peptide 1 receptor","volume":"4","author":"Redij","year":"2019","journal-title":"ACS Omega"},{"key":"B35","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/ja.2017.17","article-title":"Systems chemical biology and the antibiotic resistome","volume":"70","author":"Roemer","year":"2017","journal-title":"J. Antibiot. (Tokyo)"},{"key":"B36","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/9781394188864.ch13","article-title":"Addressing antimicrobial resistance by repurposing polyphenolic phytochemicals with novel antibacterial potential","volume-title":"Polyphenols","author":"Rudrapal","year":"2023"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.3390\/ijms21093128","article-title":"New insight into mechanisms of protein adaptation to high temperatures: a comparative molecular dynamics simulation study of thermophilic and mesophilic subtilisin-like serine proteases","volume":"21","author":"Sang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"8124","DOI":"10.3390\/ijms23158124","article-title":"The impact of plant phytochemicals on the gut microbiota of humans for a balanced life","volume":"23","author":"Santhiravel","year":"2022","journal-title":"Int. J. Moleular Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e16105","DOI":"10.7554\/eLife.16105","article-title":"Molecular dynamics-based refinement and validation for sub-5 \u00c5 cryo-electron microscopy maps","volume":"5","author":"Singharoy","year":"2016","journal-title":"ELife"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-36260-7_10","article-title":"Molecular dynamics simulations in drug discovery and pharmaceutical development","volume":"9","author":"Solo-Aben","year":"2021","journal-title":"Processes"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112153","article-title":"The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders","volume":"112153","author":"Thumann","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0266632","DOI":"10.1371\/journal.pone.0266632","article-title":"Structure-based 3D-pharmacophore modeling to discover novel interleukin 6 inhibitors: an in silico screening, molecular dynamics simulations and binding free energy calculations","volume":"17","author":"Tran","year":"2022","journal-title":"PLoS ONE"},{"key":"B45","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3389\/fchem.2020.00167","article-title":"Integrating ligand and target-driven based virtual screening approaches with in vitro human cell line models and time-resolved fluorescence resonance energy transfer assay to identify novel hit compounds against BCL-2","volume":"8","author":"Tutumlu","year":"2020","journal-title":"Front. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s11696-021-01899-y","article-title":"Novel molecules derived from 3-O-(6-galloylglucoside) inhibit main protease of SARS-CoV 2 in silico","volume":"76","author":"Umar","year":"2021","journal-title":"Chem. Pap."},{"key":"B48","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1021\/ci200454v","article-title":"Combining global and local measures for structure-based druggability predictions","volume":"52","author":"Volkamer","year":"2012","journal-title":"J. Chem. Inf. Model"},{"key":"B49","doi-asserted-by":"publisher","first-page":"10596","DOI":"10.1038\/s41598-023-37037-9","article-title":"MDTOMO method for continuous conformational variability analysis in cryo electron subtomograms based on molecular dynamics simulations","volume":"13","author":"Vuillemot","year":"2023","journal-title":"Sci. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1093\/bioinformatics\/bty707\/5085368","article-title":"admetSAR 2. 0: web-service for prediction and optimization of chemical ADMET properties","author":"Yang","year":"2018","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"862504","DOI":"10.3389\/fphar.2022.862504","article-title":"Mechanistic insights into Co-administration of allosteric and orthosteric drugs to overcome drug-resistance in T315I BCR-ABL1","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.3390\/biom12101395","article-title":"Computational dissection of the role of Trp305 in the regulation of the death-associated protein kinase\u2013calmodulin interaction","volume":"12","author":"Zhu","year":"2022","journal-title":"Biomolecules"},{"key":"B53","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3390\/ijms18050761","article-title":"3D-QSAR, molecular docking and molecular dynamics simulation of Pseudomonas aeruginosa LpxC inhibitors","volume":"18","author":"Zuo","year":"2017","journal-title":"Int. J. Mol. Sci."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2024.1411935\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:34:15Z","timestamp":1721968455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2024.1411935\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":52,"alternative-id":["10.3389\/fbinf.2024.1411935"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2024.1411935","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1411935"}}