In silico design of human IMPDH inhibitors using pharmacophore mapping and molecular docking approaches.
In silico design of human IMPDH inhibitors using pharmacophore mapping and molecular docking approaches.
复制标题
使用药效团作图和分子对接方法进行人类 IMPDH 抑制剂的计算机设计。
DOI：
10.1155/2015/418767
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发表时间：
2015
影响因子：
--
通讯作者：
Cheng MS
中科院分区：
文献类型：
--
作者：
Li RJ;Wang YL;Wang QH;Wang J;Cheng MS
肌苷5'-单磷酸脱氢酶（IMPDH）是鸟苷核苷酸从头生物合成的关键酶之一。它已成为免疫抑制、抗癌、抗病毒和抗寄生虫治疗策略中有吸引力的靶标。在这项研究中，采用药效团作图和分子对接方法来发现新型智人 IMPDH (hIMPDH) 抑制剂。 Güner-Henry (GH) 评分方法用于评估生成的药效基团假设的质量。发现所生成的药效基团假设之一的 GH 分数为 0.67。使用药效团作图方法从 ZINC 数据库中选择了 10 种潜在化合物，并将其对接至 IMPDH 活性位点。我们发现两个命中（即 ZINC02090792 和 ZINC00048033）与本研究中使用的最佳药效团特征非常匹配，并且发现它们与 IMPDH 的关键残基形成相互作用。我们认为这两种化合物是开发新型 hIMPDH 抑制剂的先导化合物。
Inosine 5′-monophosphate dehydrogenase (IMPDH) is one of the crucial enzymes in the de novo biosynthesis of guanosine nucleotides. It has served as an attractive target in immunosuppressive, anticancer, antiviral, and antiparasitic therapeutic strategies. In this study, pharmacophore mapping and molecular docking approaches were employed to discover novel Homo sapiens IMPDH (hIMPDH) inhibitors. The Güner-Henry (GH) scoring method was used to evaluate the quality of generated pharmacophore hypotheses. One of the generated pharmacophore hypotheses was found to possess a GH score of 0.67. Ten potential compounds were selected from the ZINC database using a pharmacophore mapping approach and docked into the IMPDH active site. We find two hits (i.e., ZINC02090792 and ZINC00048033) that match well the optimal pharmacophore features used in this investigation, and it is found that they form interactions with key residues of IMPDH. We propose that these two hits are lead compounds for the development of novel hIMPDH inhibitors.
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影响因子：
2.7
作者：
Dhar, TGM;Watterson, SH;Iwanowicz, EJ
通讯作者：
Iwanowicz, EJ
影响因子：
2.7
作者：
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通讯作者：
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影响因子：
5
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通讯作者：
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影响因子：
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作者：
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