Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/1054
Type: Artigo de periódico
Title: Structural modeling of high-affinity thyroid receptor-ligand complexes
Author: ARAUJO, Alexandre Suman de
MARTINEZ, Leandro
NICOLUCI, Ricardo de Paula
SKAF, Munir S.
POLIKARPOV, Igor
Abstract: Understanding the molecular basis of the binding modes of natural and synthetic ligands to nuclear receptors is fundamental to our comprehension of the activation mechanism of this important class of hormone regulated transcription factors and to the development of new ligands. Thyroid hormone receptors (TR) are particularly important targets for pharmaceuticals development because TRs are associated with the regulation of metabolic rates, body weight, and circulating levels of cholesterol and triglycerides in humans. While several high-affinity ligands are known, structural information is only partially available. In this work we obtain structural models of several TR-ligand complexes with unknown structure by docking high affinity ligands to the receptors` ligand binding domain with subsequent relaxation by molecular dynamics simulations. The binding modes of these ligands are discussed providing novel insights into the development of TR ligands. The experimental binding free energies are reasonably well-reproduced from the proposed models using a simple linear interaction energy free-energy calculation scheme.
Subject: Molecular dynamics
Nuclear receptor
Binding free energy
Thyroid hormone receptor
Thyromimetics-receptor binding modes
High affinity thyromimetics
Country: Estados Unidos
Editor: SPRINGER
Citation: EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, v.39, n.11, p.1523-1536, 2010
Rights: fechado
Identifier DOI: 10.1007/s00249-010-0610-2
Address: http://dx.doi.org/10.1007/s00249-010-0610-2
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Date Issue: 2010
Appears in Collections:IQ - Artigos e Materiais de Revistas Científicas

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