基于端粒G-四链体受体构建具有抗肿瘤功效的药效团模型  

Structure based pharmacophore modelling of telomeric G-quadruplex for anti-tumor

作　　者：王华华[1] 朱钰[1] 孙颖[1] 张婷[1] 张严[1] 

机构地区：[1]中央民族大学生命与环境科学学院,北京100081

出　　处：《计算机与应用化学》2016年第3期369-372,共4页Computers and Applied Chemistry

基　　金：中央民族大学一流大学一流学科建设项目(YDLX01013)

摘　　要：端粒G-四链体DNA是由端粒末端富含鸟嘌呤的DNA序列通过自身组装形成的一种特殊的二级结构。配体通过结合/稳定端粒G-四链体DNA可以抑制端粒酶延长端粒DNA,从而抑制了癌细胞赖以生存的端粒维持机制。本文运用Discovery Studio3.5软件中的Structure Based Pharmacophore(SBP)方法,以分子间端粒G-四链体DNA四聚体的结构为基础,构建了具有抗肿瘤功效的药效团模型。并通过分析测试集与药效团模型的匹配情况,对模型进行了验证。证明了该模型的正确性和可靠性,此药效团模型可用于天然产物数据库的高通量虚拟筛选。Telomeric G-quadruplex DNA is a kind of special DNA secondary structure formed by self-assembly of the guanine-rich sequence at the end of the telomere. Telomeric G-quadruplex ligands could inhibit the telomerase from extending the telomere through specifically binding and stabilizing this structure,thus interfering with the telomere maintenance of cancer cells which is crucial for their survival. The pharmacophore model for antitumor was constructed by Structure Based Pharmacophore （SBP） of Discovery Studio 3.5, based on the quartemary structure of intermolecular telomeric G-quadruplex DNA. By means of the matching condition analysis between test set and the pharmacophore model, the validity and reliability of the model was verified. The result indicated that the pharmacophore model can be used in the high throughput virtual screening of natural products database.

关 键 词：药效团模型 端粒G-四链体 抗肿瘤 计算机辅助药物设计 

分 类 号：TQ015.9[化学工程] TP391.9[自动化与计算机技术—计算机应用技术]