新型TPO抑制剂的计算机辅助设计与虚拟筛选  

Computer-aided Design and virtual Screening of New TPO Inhibitors

作　　者：刘燕茹[1] 于敬达[1] 李丽娜[1] 罗利霞[1] 

机构地区：[1]包头医学院,内蒙古包头014040

出　　处：《科技通报》2017年第12期230-232,共3页Bulletin of Science and Technology

摘　　要：针对当前甲状腺亢进症药物治疗存在的治愈时间长、且毒副作用大等问题,文章提出并实现了一种基于现有过氧化酶抑制剂甲亢平、甲巯咪唑、丙硫氧嘧啶以及甲硫氧嘧啶的新型TPO抑制剂的计算机辅助设计和虚拟筛选方法。首先,利用MOE软件同源模建的方法构建过氧化酶的三维结构;其次,利用MOE软件包中的分子对接获得现有抑制剂与TPO同源模版的两种结合模式,即五元硫脲嘧啶和六元咪唑环。最后,根据现有抑制剂与TPO同源模版的两种结合模式确定了一种结构修饰策略,并借助MOE软件包对先导化合物结构中部分分子片段进行了修饰。实验结果产生了两类新型TPO抑制剂候选集(共10万多种),并利用分子对接技术对设计结果进行分析和评价,发现有相当数量的分子具有极高的结合力和逆合成性,表明文中所用修饰策略是极为有效的。In view of problem such as long treatment time,much serious poisonous side effect and so on in drug treatment of hyperthyroidism,at present. A Computer-Aided Design And virtual Screening method was proposed and Realized to produce New TPO Inhibitors, which basis of the known TPO Inhibitors such as Carbimazole, methimazole, opropylthiouracil and methylthiouracil.First, 3 D structure of TPO was acquired use Homology modeling method in MOE.Second, two binding modes of TPO and Inhibitors were aquires using MOE Dock, which are five-and six-membered ring.Third. the compound optimization strategy was proposed upon inspection and analysis of the binding modes of the known TPO inhibitors, and performed by the structure-based drug design module in MOE. Following the two types of design strategy, more than100,000 candidates were generated. The design results are analyzed and evaluated by molecular docking technology,many of which display high potency and synthetic feasibility, witch indicating the strategy is effective.

关 键 词：过氧化酶 同源建模 分子对接 计算机辅助设计 虚拟筛选 

分 类 号：TP391.41[自动化与计算机技术—计算机应用技术] R914.2[自动化与计算机技术—计算机科学与技术]