{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:21:29Z","timestamp":1792804889113,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Basic Science Institute (National Research Facilities and Equipment Center)","award":["2022R1A6C101A739"],"award-info":[{"award-number":["2022R1A6C101A739"]}],"id":[{"id":"https:\/\/ror.org\/0417sdw47","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malaria remains a global health challenge, with increasing resistance to frontline antimalarial treatments such as artemisinin (ART) threatening the efficacy of current therapies. In this study, we investigated the potential of FDA-approved drugs to selectively inhibit the malarial proteasome, a novel target for antimalarial drug development. By leveraging pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations, and binding free-energy calculations, we screened a library of compounds to identify inhibitors selective for the Plasmodium proteasome over the human proteasome. Our results highlighted Argatroban, LM-3632, Atazanavir Sulfate, and Pemetrexed Hydrate as promising candidates, with Argatroban and Pemetrexed Hydrate showing the highest binding affinity and selectivity toward the malarial proteasome. MD simulation and gmx_MMPBSA analysis confirmed the compounds\u2019 ability to remain within the active site of the malarial proteasome, while some exited or exhibited reduced stability within the human proteasome. This study underscores the potential of proteasome-targeting drugs for overcoming malarial drug resistance and paves the way for the further optimization of these compounds.<\/jats:p>","DOI":"10.3390\/ijms252211881","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T08:25:14Z","timestamp":1730795114000},"page":"11881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of Malaria-Selective Proteasome \u03b25 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"25","author":[{"given":"Muhammad","family":"Yasir","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Taek","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-6675","authenticated-orcid":false,"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-3545","authenticated-orcid":false,"given":"Wanjoo","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12936-021-03599-0","article-title":"Achieving global malaria eradication in changing landscapes","volume":"20","author":"Fornace","year":"2021","journal-title":"Malar. 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