通过引导分子动力学研究视黄酸与其受体的解离。
Unbinding of retinoic acid from its receptor studied by steered molecular dynamics.
作者信息
Kosztin D, Izrailev S, Schulten K
机构信息
Departments of Chemistry and Physics, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 USA.
出版信息
Biophys J. 1999 Jan;76(1 Pt 1):188-97. doi: 10.1016/S0006-3495(99)77188-2.
Abstract
Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by conformational changes in the protein which induce transactivation or transrepression of the target genes. In this paper we present a study of the hormone binding/unbinding process in order to clarify the role of some of the amino acid contacts and identify possible pathways of the all-trans retinoic acid binding/unbinding to/from human retinoic acid receptor (hRAR)-gamma. Three possible pathways were explored using steered molecular dynamics simulations. Unbinding was induced on a time scale of 1 ns by applying external forces to the hormone. The simulations suggest that the hormone may employ one pathway for binding and an alternative "back door" pathway for unbinding.
摘要
维甲酸受体（RAR）是一种依赖配体的转录因子，可调节参与细胞生长、分化和发育的基因的表达。维甲酸激素与RAR的结合伴随着蛋白质的构象变化，这种变化会诱导靶基因的反式激活或反式抑制。在本文中，我们进行了一项关于激素结合/解离过程的研究，以阐明一些氨基酸接触的作用，并确定全反式维甲酸与人维甲酸受体（hRAR）-γ结合/解离的可能途径。使用引导分子动力学模拟探索了三种可能的途径。通过对激素施加外力，在1纳秒的时间尺度上诱导解离。模拟结果表明，激素可能采用一种途径进行结合，而采用另一种“后门”途径进行解离。
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