Models for the binding of amiodarone to the thyroid hormone receptor

David K. Chalmers, Sharon L.A. Munro, David J. Craik

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The antiarrhythmic drug amiodarone has recently been characterized as the first known thyroid hormone antagonist. Its mode of interaction with the thyroid hormone receptor is therefore of interest. A computational analysis of the conformational flexibility of amiodarone using molecular mechanics and the semiempirical molecular orbital method AM1 has been performed. The molecular mechanics studies show that the low-energy conformations of the benzoylbenzofuran portion of amiodarone can be grouped into 4 distinct classes, while the diethylaminoethoxy side chain is extremely flexible. Conformers representative of the 4 low-energy classes were fitted to an extended thyroid hormone receptor model. Four independent modes in which amiodarone could bind to the thyroid hormone receptor site were evaluated.

Original languageEnglish
Pages (from-to)19-31
Number of pages13
JournalJournal of Computer-Aided Molecular Design
Issue number1
Publication statusPublished - 1 Feb 1992
Externally publishedYes


  • Conformational search
  • Molecular graphics
  • Molecular mechanics
  • Semiempirical molecular orbital calculations

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