17α取代雌二醇与雌激素受体结合活性的定量构效关系研究

Quantum chemistry study of QSAR between the relative binding affinities and 17αsubstituted estradiol

应用分子力学法MM_+和半经验量子化学AM1法几何全优化得到29个17α取代雌二醇衍生物的优势构象,再利用量子化学法和分子图形学技术获得相应优势构象的电子结构参数和几何结构参数,采用多元线性回归分析研究17α取代雌二醇衍生物与雌激素受体结合活性(relative binding affinities)的定量构效关系。结果表明17α取代雌二醇衍生物与雌激素受体结合活性和分子键合能(BE)、17号碳原子的净电荷(Q)及7号和8号碳原子间键长的相关性较好,成功地建立了29个17α取代雌二醇衍生物的构效关系式,所建回归方程的复相关系数R^2及去一法交互检验相关系数R_(CV)~2分别为0.890和0.712。

To analyze the QSAR of 29 17α substituted estradiols, MM ＋ molecular mechanics method and semi-empirical AM1 method were performed. Using multivariate linear regression analysis, the authors obtained a significant QSAR. It could be concluded as follows：the relative binding affinities of 17v substituted estradiols with ER were highly correlated with the binding energy, the net charge of C17 and the bond length between C7 and Cs. The correlation coefficient square and cross validation using leaving one out（LOO） of successful QSAR with correlation for 29 17α substituted estradiols were 0. 890 and 0. 712, respectively.