{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:00:49Z","timestamp":1784869249042,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aces.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry \u0097 An Asian Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The growing demand for new therapeutics highlights the need for intelligent, cost\u2010effective, and scalable drug discovery strategies. Here, we present an artificial intelligence (AI)\u2010based ensemble framework to accelerate the identification of small\u2010molecule inhibitors against therapeutic targets. As a case study, we applied this approach to HIV\u20101 reverse transcriptase (HIV\u20101 RT), an essential enzyme in viral replication. Our stacking ensemble model, trained on a curated ChEMBL dataset, achieved high predictive performance (90.3% accuracy, 89.4% ROC\u2010AUC) and was used to screen the Natural Products Atlas (NPA) database. Promising hits were evaluated through physicochemical and ADMET filters, molecular docking, and 1 \u00b5s molecular dynamics (MD) simulations. Compound NP1, which exhibited stable binding to the NNRTI binding pocket, outperformed the FDA\u2010approved drug doravirine in post\u2010MD characterizations. Network analysis further suggested potential allosteric regulation via residues N136 and E138. This flexible AI\u2010MD pipeline provides an efficient strategy for discovering and repurposing inhibitors, with broad applicability to other therapeutic targets.<\/jats:p>","DOI":"10.1002\/asia.70340","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:30:07Z","timestamp":1759174207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Robust Ensemble Machine Learning Approach for Inhibitor Discovery: Case Study of HIV\u20101 NNRTI and Validation Using MD Simulation"],"prefix":"10.1002","volume":"21","author":[{"given":"Anvesha","family":"Shree","sequence":"first","affiliation":[{"name":"Physical and Biomolecular Research Lab Department of Chemical Sciences Indian Institute of Science Education and Research (IISER) Berhampur  Ganjam Odisha 760010 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratyush","family":"Pani","sequence":"additional","affiliation":[{"name":"Physical and Biomolecular Research Lab Department of Chemical Sciences Indian Institute of Science Education and Research (IISER) Berhampur  Ganjam Odisha 760010 India"},{"name":"Department of Biological Sciences Indian Institute of Science Education and Research (IISER) Berhampur  Ganjam Odisha 760010 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-8220","authenticated-orcid":false,"given":"Malay Kumar","family":"Rana","sequence":"additional","affiliation":[{"name":"Physical and Biomolecular Research Lab Department of Chemical Sciences Indian Institute of Science Education and Research (IISER) Berhampur  Ganjam Odisha 760010 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6189183"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.041807.123549"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162704"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0753-3322(99)80063-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006882"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.11.009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.10.071"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1707186"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/327716a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.60.2.771-775.1986"},{"key":"e_1_2_8_11_1","first-page":"411","volume":"15","author":"Ashley D. 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