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采用比较分子力场方法(CoMFA)及分子对接方法对一系列雌二醇衍生物的3D-QSAR及其与受体作用方式进行研究,建立了3D-QSAR的CoMFA模型,获得了化合物的相对亲合力RBA(Relative Binding Affinity)与静电场及立体场分布之间的关系;CoMFA模型的统计学参数为:q~2=0.667,r~2=0.939,SD=0.280,F=49.033,立体场与静电场的贡献分别为56.8%和41.6%。相对亲合力小的化合物一般带有较大的取代基,其对接能量得分较低;相对亲合力大的化合物一般带有较小的取代基,其对接能量得分较高。化合物的对接能量得分和相对亲合力之间有良好的线性关系,其线性相关系数R为0.890。活性口袋周围的环境也与3D-QSAR的立体场分布相匹配。对接结果还显示这类化合物和雌激素的结合主要是通过氢键作用来实现,即3-OH与R394上的氨基以及17-OH与受体残基H524咪唑环上的氮形成的氢键。
The 3D-QSAR and its interaction with a series of estradiol derivatives were studied by the method of comparative molecular force field (CoMFA) and molecular docking, and the CoMFA model of 3D-QSAR was established. The relative relatives of the compounds The relationship between electrostatic force distribution and electrostatic field and the distribution of electrostatic fields is as follows: the statistical parameters of CoMFA model are: q ~ 2 = 0.667, r ~ 2 = 0.939, SD = 0.280 and F = 49.033. The contribution of the electrostatic field is 56.8% and 41.6% respectively. Relatively low affinity compounds generally have larger substituents with lower docking energy scores; relatively high affinity compounds typically have smaller substituents with higher docking energy scores. There was a good linear relationship between docking energy score and relative affinity of the compound with a linear correlation coefficient R of 0.890. The environment around the active pocket also matches the 3D field distribution of the 3D-QSAR. Docking results also show that the binding of such compounds to estrogens occurs primarily through hydrogen bonding, that is, the hydrogen bond between the 3-OH and R394 amino groups and the nitrogen on the 17-OH and the acceptor H524 imidazole ring.