化学学报 ›› 2001, Vol. 59 ›› Issue (11): 1925-1931. 上一篇    下一篇

研究论文

维甲化合物与维甲X受体相互作用模拟及QSAR研究

郭宗儒;易翔;王敏敏;褚凤鸣   

  1. 中国医学科学院药物研究所.北京(100050)
  • 发布日期:2001-11-15

Molecular modeling and QSAR studies on the interaction mechanism of retinoids binding to RXR

Guo Zongru;Yi Xiang;Wang Minmin;Chu Fengming   

  1. Inst Mat Med, Chinese Acad Med Sci.Beijing(100050)
  • Published:2001-11-15

用分子对接确定了一系列RXR激动剂与受体的作用方式,与X衍射测得的晶体复合物中9-cis-RA的作用方式相近。对接后的配体-受体复和物经分子力学优化后更接近药效构象,两者相互作用能与活性具有一定的相关性,相关系数R^2=0.64。用活性构象建立的CoMFA模型比低能构象建立的CoMFA模型有更高的可信度,其交叉验证相关系q^2=0.791,非交叉验证相关系数γ^2=0.988,绝对误差SE=0.099,f6,33=456.8。

关键词: 维甲化合物, 维甲X核受体, 相互作用, RXR激动剂, 分子对接, 定量构效关系

Retioid X receptors (RXRs) play a critical role in the regulation of many biological activities and their specific agonists, including oxime ligands, functionally activate both homodimer RXR: RXR and heterodimer RXR:PPAR, the later relates to insulin sensitization and has a potential application in the treatment of type Ⅱdiabeter. Based on RXR and 9-cis-RA complex crystallographic data, interaction between these compounds and RXR are simulated with DOCK 4.0. After minimizing each ligand -receptor complex, from resulting energy and activity an equations is deduced with the correlation coefficient R^2=0.64. Two CoMFA models are built and compared. One model originates from the ligand conformation extracted directly from complex, the other from energy -minimized ligands. The higher significance of the former than that of the later suggests that the conformation from induced fit of receptor be more reliable.

Key words: INTERACTIONS, QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP

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