{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:04:25Z","timestamp":1790593465054,"version":"4.1.0"},"reference-count":59,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroid hormone receptors (TRs) play a critical role in human development, growth, and metabolism. Antagonists of TRs offer an attractive strategy to treat hyperthyroidism without the disadvantage of a delayed onset of drug action. While it is challenging to examine the atomistic behavior of TRs in a laboratory setting, computational methods such as molecular dynamics (MD) simulations have proven their value to elucidate ligand-induced conformational changes in nuclear receptors. Here, we performed MD simulations of TR\u03b1 and TR\u03b2 complexed to their native ligand triiodothyronine (T3) as well as several antagonists. Based on the examination of 27 \u03bcs MD trajectories, we showed how binding of these compounds influences various structural features of the receptors including the helicity of helices 3 and 10 as well as the location of helix-12. Helices 3 and 12 are known to mediate coactivator association required for downstream signaling, suggesting these changes to be the molecular basis for TR antagonism. A mechanistic analysis of the trajectories revealed an allosteric pathway between H3 and H12 to be responsible for the conformational adaptations. Even though a mechanistic understanding of conformational adaptations triggered by TR antagonists is important for the development of novel therapeutics, they have not been previously examined in detail as it was done here.<\/jats:p>","DOI":"10.1021\/acs.jcim.0c01403","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T15:33:54Z","timestamp":1610724834000},"page":"1010-1019","source":"Crossref","is-referenced-by-count":9,"title":["Conformational Changes of Thyroid Receptors in Response\nto Antagonists"],"prefix":"10.1021","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-2324","authenticated-orcid":true,"given":"Andre\u0301","family":"Fischer","sequence":"first","affiliation":[{"name":"University of Basel , , Klingelbergstrasse 61 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Frehner","sequence":"additional","affiliation":[{"name":"University of Basel , , Klingelbergstrasse 61 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-5188","authenticated-orcid":true,"given":"Markus A.","family":"Lill","sequence":"additional","affiliation":[{"name":"University of Basel , , Klingelbergstrasse 61 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2758-2680","authenticated-orcid":true,"given":"Martin","family":"Smies\u030cko","sequence":"additional","affiliation":[{"name":"University of Basel , , Klingelbergstrasse 61 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"2026092806084265100_cit1","first-page":"147","volume-title":"Vitamins and Hormones","author":"Mackenzie","year":"2018","edition":"1"},{"key":"2026092806084265100_cit2","doi-asserted-by":"publisher","first-page":"3258","DOI":"10.2174\/092986709788803277","article-title":"Thyroid Hormone\nAntagonists: Potential Medical Applications and Structure Activity\nRelationships","volume":"16","author":"Malm","year":"2009","journal-title":"Curr. 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