(1,3)-β-D-葡聚糖合成酶小分子抑制剂药效团模型的构建
投稿时间:2017-08-20  修订日期:2018-01-19  点此下载全文
引用本文:姜艳娟,崔俐俊,贺潇蒙,刘娜,盛春泉.(1,3)-β-D-葡聚糖合成酶小分子抑制剂药效团模型的构建[J].药学实践杂志,2018,36(2):116~120
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作者单位E-mail
姜艳娟 福建中医药大学, 福建 福州 350122
第二军医大学药学院, 上海 200433 
 
崔俐俊 上海健康医学院药学院, 上海 201318  
贺潇蒙 第二军医大学药学院, 上海 200433  
刘娜 第二军医大学药学院, 上海 200433 liuna66@aliyun.com 
盛春泉 福建中医药大学, 福建 福州 350122
第二军医大学药学院, 上海 200433 
shengcq@hotmail.com 
基金项目:国家自然科学基金面上项目(81573283);国家自然科学基金青年基金项目(21502224)
中文摘要:目的 开展基于配体的计算机辅助药物设计,构建(1,3)-β-D-葡聚糖合成酶[(1,3)-β-D-Glucan Synthase,GS]小分子抑制剂的药效团模型。方法 选取结构多样、抑酶活性较好的6个小分子构成训练集,利用Catalyst的药效团生成模块中的HipHop算法构建药效团模型,用构建的Decoyset 3D数据库对药效团模型进行评估。结果 药效团模型(pharmacophore)02具有较好的富集率因子以及敏感性、特异性参数。用Decoyset 3D数据库对药效团模型进行验证,该模型具有较好的区分能力。结论 本课题开展基于活性配体的GS小分子抑制剂药效团构建,对新型小分子GS抑制剂的设计和发现具有一定的指导意义。
中文关键词:小分子抑制剂  药效团模型  药物设计  配体
 
The construction of pharmacophore model for (1,3)-β-D-glucan synthase small molecule inhibitors
Abstract:Objective To perform the ligand-based computer-aided drug design and construct the pharmacophore model of (1,3)-β-D-Glucan Synthase (GS) small molecule inhibitors. Method Six small molecules with diverse structures and good inhibitory activity were selected to construct the training set. The HipHop algorithm in Catalyst pharmacophore generation module was utilized to construct the pharmacophore models. The pharmacophore models were evaluated by constructed Decoyset 3D database. Results Pharmacophore 02 has a good enrichment factor, sensitivity and specificity parameters. Pharmacophore model validation with Decoyset 3D database proved that the model has good distinguishing capability. Conclusion The pharmacophore model of GS small molecule inhibitors was constructed and tested. It will provide valuable information for design and discovery of novel small molecule GS inhibitors.
keywords:small molecule inhibitors  pharmacophore model  drug design  ligand
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