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This research aims to pinpoint the potential drug candidates targeting\n                    <jats:italic>Mtb<\/jats:italic>\n                    methionyl\u2010tRNA synthetase (\n                    <jats:italic>Mtb<\/jats:italic>\n                    MetRS) using\n                    <jats:italic>in silico<\/jats:italic>\n                    techniques. Employing machine learning algorithms, including Random Forest, Extra Trees, and Nu\u2010Support Vector, a voting classifier was built to screen 10 million molecules. A total of 590 molecules were filtered and analyzed for mutagenicity and other toxicities, resulting in 169 candidates for molecular docking. Among these, 1\u2010[4\u2010(1,3\u2010benzodioxol\u20105\u2010ylmethyl)piperazin\u20101\u2010yl]\u20102\u2010phenylsulfanylethanone (L1) and 1\u2010ethyl\u20106\u2010fluoro\u20104\u2010oxo\u20107\u2010(4\u2010pentanoylpiperazin\u20101\u2010yl)quinoline\u20103\u2010carboxylic acid (L2) demonstrated strong binding affinities (\u221212.74\u2005kcal\/mol for L1 and \u221211.83\u2005kcal\/mol for L2) and favorable pharmacokinetic properties. MM\/PBSA, DFT calculations, and LD\n                    <jats:sub>50<\/jats:sub>\n                    values supported their stability, reactive nature, and safer toxicity profile, respectively. L1 and L2 are investigated as potential inhibitors of\n                    <jats:italic>Mtb<\/jats:italic>\n                    MetRS; however, additional\n                    <jats:italic>in\u2005vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u2005vivo<\/jats:italic>\n                    investigations are necessary to confirm these findings.\n                  <\/jats:p>","DOI":"10.1002\/open.202400460","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:37:36Z","timestamp":1740530256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Machine Learning\u2010Based High\u2010Throughput Screening, Molecular Modeling and Quantum Chemical Analysis to Investigate\n                    <i>Mycobacterium tuberculosis<\/i>\n                    MetRS Inhibitors"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4839-0875","authenticated-orcid":false,"given":"Rajesh","family":"Maharjan","sequence":"first","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8048-2141","authenticated-orcid":false,"given":"Kalpana","family":"Gyawali","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3623-0436","authenticated-orcid":false,"given":"Arjun","family":"Acharya","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9680-2982","authenticated-orcid":false,"given":"Madan","family":"Khanal","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9501-0928","authenticated-orcid":false,"given":"Kamal","family":"Khanal","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5200-190X","authenticated-orcid":false,"given":"Mohan Bahadur","family":"Kshetri","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-4008","authenticated-orcid":false,"given":"Madhav Prasad","family":"Ghimire","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-0808","authenticated-orcid":false,"given":"Tika Ram","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Central Department of Physics Tribhuvan University  Kathmandu 44600 Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10121990"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115646"},{"key":"e_1_2_9_3_1","volume":"73","author":"Williams P. 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