{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:19:48Z","timestamp":1772252388346,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Stearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases, including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as an apoprotein. The modeling of SCD1:fatty acid interactions suggests that: (1) SCD1:CoA moiety interactions open the substrate-binding tunnel, (2) SCD1 stabilizes a substrate conformation favorable for desaturation, and (3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.<\/jats:p>","DOI":"10.3390\/biom11101435","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sequential Dynamics of Stearoyl-CoA Desaturase-1(SCD1)\/Ligand Binding and Unbinding Mechanism: A Computational Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Anna B.","family":"Petroff","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4323-7572","authenticated-orcid":false,"given":"Rebecca L.","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Yates","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, The University of Mississippi School of Pharmacy, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph D.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerome","family":"Baudry","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.tem.2017.10.003","article-title":"Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism","volume":"28","author":"Syed","year":"2017","journal-title":"Trends Endocrinol. 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