黄酮类化合物与雌激素受体作用的三维定量构效关系

黄酮类化合物是一种普遍存在于食物和植物中的内分泌干扰物. 选取20个典型的黄酮类化合物, 采用基于分子对接(docking)的比较分子场分析法(CoMFA)和比较分子相似性指数(CoMSIA)方法, 研究它们与雌激素受体(ER?)的相互作用, 建立了这些黄酮类化合物和雌激素受体之间的三维定量构效关系(QSAR)模型, 得到CoMFA模型的最佳交互验证相关系数Q²_LOO为0.845, 非交互验证相关系数R²为0.988, 相应的CoMSIA模型的交互验证相关系数Q²_LOO为0.670, 非交互验证相关系数R²为0.990, 说明模型具有很强的稳定性和预测能力. 此外, 分子对接结果揭示了受体腔中的关键残基及其与黄酮类化合物作用的具体方式.

Three-dimensional quantitative structure activity relationship of flavonoids and estrogen receptor based on docking

Flavonoids are endocrine disrupting compounds that occur ubiquitously in foods of plant origin. The 3D-QSAR model based on ligand-receptor docking is established between 20 flavonoids and estrogen receptor alpha (ERα), which may provide further theoretical basis for researching relationship between flavones and estrogen. Comparative molecular field analysis (CoMFA) was employed and the best result of cross-validation and non cross validation were 0.845 and 0.988, respectively. Correspondingly, molecular similarity index analysis (CoMSIA) was employed and the result of cross-validation and non cross validation were 0.670 and 0.990, respectively. The CoMFA /CoMSIA and docking results revealed the structural features for estrogen activity and key amino acid residues in binding pocket, and provided an insight into the interaction between the ligands and these amino acid results.