雌激素β受体喹啉类配体的分子对接及3D-QSAR研究

对33个喹啉衍生物的雌激素β受体活性进行了分子对接以及比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA). 对接结果显示氢键和疏水作用是配体与受体结合的主要因素，同时结果亦显示对接结合能与观测值pIC50具有极显著的线性相关性. 根据对接后各优势构象将33个样本进行叠合并进行CoMFA与CoMSIA研究，均得到了较优的结果，其中以选用立体场、静电场和疏水场建立的CoMSIA模型结果最优，其主成分数，r2，q2（LOO）和r2pred分别为2, 0.894, 0.708和0.802. 构效关系模型分析显示基团的空间位阻、电性及疏水作用是影响活性的主要因素

Molecular Docking and 3D-QSAR Research of Quinoline De-rivatives as Estrogen Receptor β Ligands

The molecular docking followed by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was employed to the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of estrogen receptor-β of 33 quinoline derivatives. A significant correlation coefficient was obtained between total scores and binding affinities. The results showed that the hydrogen-bonding interactions between the hydroxy group of chromane and quinoline ring and the receptor, hydrophobic interactions between the ligand and the active site of estrogen receptor-β, and electronic interactions between the ligand and the Arg346 and Glu305 residuals were the dominant factors affecting the binding affinities. Besides, the steric effect of substituting group of quinoline ring also affected the binding activities. Based on the docking conformations, CoMFA and CoMSIA were employed to the QSAR studies of 33 quinoline derivatives. The number of principal components, r2, q2 (leave-one-out, LOO), of the optimal CoMSIA model were 6, 0.958, 0.669 and 0.741 respectively. The conclusions obtained from contour map analysis were in agreement with the docking results.