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This study integrates subtractive proteomics and ensemble docking to identify and characterize essential proteins in P. aeruginosa, aiming to discover therapeutic targets and repurpose commercial existing drugs. Using subtractive proteomics, we refined the dataset to discard redundant proteins and minimize potential cross-interactions with human proteins and the microbiome proteins. We identified 12 key proteins, including a histidine kinase and members of the RND efflux pump family, known for their roles in antibiotic resistance, virulence, and antigenicity. Predictive modeling of the three-dimensional structures of these RND proteins and subsequent molecular ensemble-docking simulations led to the identification of MK-3207, R-428, and Suramin as promising inhibitor candidates. These compounds demonstrated high binding affinities and effective inhibition across multiple metrics. Further refinement using non-covalent interaction index methods provided deeper insights into the electronic effects in protein\u2013ligand interactions, with Suramin exhibiting superior binding energies, suggesting its broad-spectrum inhibitory potential. Our findings confirm the critical role of RND efflux pumps in antibiotic resistance and suggest that MK-3207, R-428, and Suramin could be effectively repurposed to target these proteins. This approach highlights the potential of drug repurposing as a viable strategy to combat P. aeruginosa infections.<\/jats:p>","DOI":"10.3390\/ijms25158027","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T14:26:50Z","timestamp":1721744810000},"page":"8027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["From Proteome to Potential Drugs: Integration of Subtractive Proteomics and Ensemble Docking for Drug Repurposing against Pseudomonas aeruginosa RND Superfamily Proteins"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3871-0261","authenticated-orcid":false,"given":"Gabriela","family":"Urra","sequence":"first","affiliation":[{"name":"Laboratorio de Bioinform\u00e1tica y Qu\u00edmica Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Vald\u00e9s-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Doctorado en Biotecnolog\u00eda Traslacional, Facultad de Ciencias Agrarias y Forestales, Universidad Cat\u00f3lica del Maule, Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-9020","authenticated-orcid":false,"given":"Reynier","family":"Suardiaz","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica F\u00edsica, Facultad de Ciencias Qu\u00edmicas, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erix W.","family":"Hern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioinform\u00e1tica y Qu\u00edmica Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3480094, Chile"},{"name":"Unidad de Bioinform\u00e1tica Cl\u00ednica, Centro Oncol\u00f3gico, Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-1907","authenticated-orcid":false,"given":"Jonathan M.","family":"Palma","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad de Talca, Curic\u00f3 3344158, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda E.","family":"R\u00edos-Rozas","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioinform\u00e1tica y Qu\u00edmica Computacional, Departamento de Medicina Traslacional, Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3480094, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila A.","family":"Flores-Morales","sequence":"additional","affiliation":[{"name":"Mag\u00edster en Ciencias de la Computaci\u00f3n, Universidad Cat\u00f3lica del Maule, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Alegr\u00eda-Arcos","sequence":"additional","affiliation":[{"name":"N\u00facleo de Investigaci\u00f3n en Data Science, Facultad de Ingenier\u00eda y Negocios, Universidad de las Am\u00e9ricas, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-9353","authenticated-orcid":false,"given":"Osvaldo","family":"Y\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"N\u00facleo de Investigaci\u00f3n en Data Science, Facultad de Ingenier\u00eda y Negocios, Universidad de las Am\u00e9ricas, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-1989","authenticated-orcid":false,"given":"Luis","family":"Morales-Quintana","sequence":"additional","affiliation":[{"name":"Multidisciplinary Agroindustry Research Laboratory, Instituto de Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Cinco Pte. 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