新型TPO抑制剂的计算机辅助设计与虚拟筛选
发布时间：2019-06-10 06:14
【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。
[Abstract]:In view of the problems existing in the drug treatment of hyperthyroidism, such as long cure time and great toxic and side effects, this paper proposes and implements a kind of hyperthyroidism inhibitor hyperthyroidism, methimidazole, which is based on the existing peroxide inhibitor hyperthyroidism. Computer aided design and virtual screening method for novel TPO inhibitors of propylthiouracil and methionine. Firstly, the three-dimensional structure of peroxide was constructed by MOE software homologous modeling. Secondly, two binding modes of inhibitor and TPO homologous template, five-member thiouracil and six-element imidazolium ring, were obtained by molecular docking in MOE software package. Finally, a structural modification strategy was determined according to the two binding modes of the existing inhibitor and TPO homologous template, and some molecular fragments in the structure of the lead compound were modified by MOE software package. The experimental results show that two kinds of new TPO inhibitor candidate sets (more than 100000 kinds) are produced, and the design results are analyzed and evaluated by molecular docking technique. It is found that a considerable number of molecules have very high binding and inverse synthesis. It is shown that the modification strategy used in this paper is very effective.
【作者单位】： 包头医学院;
【分类号】：R91;TP391.72
[Abstract]:In view of the problems existing in the drug treatment of hyperthyroidism, such as long cure time and great toxic and side effects, this paper proposes and implements a kind of hyperthyroidism inhibitor hyperthyroidism, methimidazole, which is based on the existing peroxide inhibitor hyperthyroidism. Computer aided design and virtual screening method for novel TPO inhibitors of propylthiouracil and methionine. Firstly, the three-dimensional structure of peroxide was constructed by MOE software homologous modeling. Secondly, two binding modes of inhibitor and TPO homologous template, five-member thiouracil and six-element imidazolium ring, were obtained by molecular docking in MOE software package. Finally, a structural modification strategy was determined according to the two binding modes of the existing inhibitor and TPO homologous template, and some molecular fragments in the structure of the lead compound were modified by MOE software package. The experimental results show that two kinds of new TPO inhibitor candidate sets (more than 100000 kinds) are produced, and the design results are analyzed and evaluated by molecular docking technique. It is found that a considerable number of molecules have very high binding and inverse synthesis. It is shown that the modification strategy used in this paper is very effective.
【作者单位】： 包头医学院;
【分类号】：R91;TP391.72
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