摘要
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 comparison molecular field （CoMFA） and molecular docking method was used to study the 3D-QSAR of a serial of estradiol derivatives and the characteristics of the binding active site. A reliable 3D-QSAR CoMFA model was established. The CoMFA statis- tic parameters are q^2 =0. 667, r^2 =0. 939, SD =0. 280, F =49. 033. Docking results showed that the compounds with larger substituents had lower energy score, small substituents had higher energy score and the structure of the binding site is in agreement with the steric field contour of CoMFA. The energy scores and the corresponding IogRBA values have a significant correlation, in which the correlation coefficient R is 0. 890. Docking results also revealed the binding interactions of these kind of compounds and estrogen receptor mainly came from the hydrogen bonds, namely between hydroxyl group of site 3 and R394 as well as the hydroxyl group of site 17 and H524.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2008年第12期1511-1516,共6页
Computers and Applied Chemistry
基金
国家自然科学基金资助项目(90608012)
