【摘要】：針對當前甲狀腺亢進癥藥物治療存在的治愈時間長、且毒副作用大等問題,文章提出并實現(xiàn)了一種基于現(xiàn)有過氧化酶抑制劑甲亢平、甲巰咪唑、丙硫氧嘧啶以及甲硫氧嘧啶的新型TPO抑制劑的計算機輔助設計和虛擬篩選方法。首先,利用MOE軟件同源模建的方法構建過氧化酶的三維結構;其次,利用MOE軟件包中的分子對接獲得現(xiàn)有抑制劑與TPO同源模版的兩種結合模式,即五元硫脲嘧啶和六元咪唑環(huán)。最后,根據現(xiàn)有抑制劑與TPO同源模版的兩種結合模式確定了一種結構修飾策略,并借助MOE軟件包對先導化合物結構中部分分子片段進行了修飾。實驗結果產生了兩類新型TPO抑制劑候選集(共10萬多種),并利用分子對接技術對設計結果進行分析和評價,發(fā)現(xiàn)有相當數(shù)量的分子具有極高的結合力和逆合成性,表明文中所用修飾策略是極為有效的。
[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.
【作者單位】： 包頭醫(yī)學院;
【分類號】：R91;TP391.72

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