摘要
采用Topomer CoMFA方法对21个6-(1-萘甲基)取代S-DABO类化合物进行三维定量构效关系研究,建立了3D-QSAR模型,所得优化模型的主要参数分别为N=3,q^2=0.659,r^2=0.917,F=44.418,SEE=0.222,q_(stderr)~2=0.45,r_(stderr)~2=0.22.结果表明,该模型具有良好的稳定性及预测能力.采用Topomer search在ZINC分子数据库中进行R基团的虚拟筛选,设计了8个活性优于模板分子的新化合物.借助Surflex-dock分子对接研究了新化合物与HIV-1逆转录酶作用模式与机制.结果显示,新化合物与HIV-1逆转录酶的LYS101、LYS103、TYR318位点作用显著.
Topomer CoMFA was used to build a three dimensional quantitative structure ac tivity relationship（3D QSAR） model for 21 6 napthylmethyl substituted S DABO analogues in this paper,with key parameters as follows：N=3,q2 =0. 659,r2 =0. 917,F=44. 418,SEE = 0. 222, q2stders= 0.45, r2stders = 0.22, respectively. The result showed that this model had a good stability and a predictive ability. Topomer search was employed to select R group in ZINC molecular database; as a result,a total of 8 new compounds with better activity than tern plate molecules were designed. Then, we explored that interaction mode between the new compounds and the HIV 1 reverse transcriptase acceptor using Surflex dock. The results suggest that the new compounds obviously with LYS101.LYS103.TYR318 sites of HIV 1 reverse transcriptase.
作者
仝建波
王洋
雷珊
秦尚尚
TONG Jian-bo;WANG Yang;LEI Shan;QIN Shang-shang(College of Chemistry and Chemical Engineering,Shaanxi Key Laboratory of Chemical Additives for Industry,Shaanxi University of Science ＆ Technology,Xi＇an 710021,China)
出处
《陕西科技大学学报》
CAS
2018年第6期63-70,92,共9页
Journal of Shaanxi University of Science & Technology
基金
国家自然科学基金项目(21275094
21475081)
陕西科技大学研究生创新基金项目
