{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:18:44Z","timestamp":1787548724873,"version":"build-2736575974"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CAD"],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"\n Introduction:<\/jats:title>\n HMG-CoA reductase (HMGCR) is a validated lipid-lowering target,\nbut statin intolerance, variable response, and drug-drug interactions justify exploration of mechanistically\ndistinct modulators. This study prioritized approved drugs that may bind predicted\nnon-orthosteric HMGCR pockets.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n A computational workflow combining homology modeling (SWISS-MODEL;\nGMQE = 0.95), CB-Dock pocket detection, AutoDock Vina docking, 100 ns all-atom molecular\ndynamics (MD) simulations (GROMACS 2023.2), MM\/PBSA binding-free-energy estimation,\nand in silico ADMET screening was applied to Fluspirilene, Lenvatinib, Siponimod, and Lumacaftor.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Two putative non-orthosteric pockets were identified with calculated volumes of 394\n\u00c53 (Pocket 1) and 305 \u00c53 (Pocket 2). Fluspirilene showed the most favorable Pocket 1 docking\nscore (-9.4 kcal\/mol) and MM\/PBSA binding-free-energy estimate (-65.2 \u00b1 3.8 kcal\/mol),\nwhereas Lumacaftor showed the most favorable Pocket 2 score (-8.9 kcal\/mol; MM\/PBSA:\n-55.7 \u00b1 4.1 kcal\/mol). MD trajectories supported retention of the selected poses throughout the\n100 ns simulation window.<\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n The predicted interactions involved hydrophobic contacts, \u03c0-associated interactions,\nhydrogen bonding, and electrostatic contacts at sites spatially distinct from the canonical\nstatin\/HMG-CoA catalytic region. These findings support a non-orthosteric binding hypothesis\nbut do not establish functional allosteric inhibition without enzyme kinetics, direct binding assays,\nand structural validation.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n The study identifies computationally prioritized candidate scaffolds for putative\nnon-orthosteric HMGCR modulation and defines the biochemical, kinetic, and structural validation\nrequired before any therapeutic interpretation.<\/jats:p>\n <\/jats:sec>","DOI":"10.2174\/0115734099490379260809123720","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:21:01Z","timestamp":1787545261000},"update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Identification of Potential HMG-CoA Reductase Modulators Through Drug Repurposing: Structural Insights and Therapeutic\nImplications"],"prefix":"10.2174","volume":"22","author":[{"given":"Qusay Abdulsattar","family":"Mohammed","sequence":"first","affiliation":[{"name":"College of Dentistry, University of Al-Maarif, Ramadi, 31001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5391-846X","authenticated-orcid":true,"given":"Mohammed R\u2060.","family":"Al-Shaheen","sequence":"additional","affiliation":[{"name":"College of Dentistry, University of Al-Maarif, Ramadi, 31001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","container-title":["Current Computer-Aided Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0115734099490379260809123720","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/257244\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0115734099490379260809123720","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:21:03Z","timestamp":1787545263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/257244\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":0,"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0115734099490379260809123720","relation":{},"ISSN":["1573-4099"],"issn-type":[{"value":"1573-4099","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2026-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}