| Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study | |
Li, Yingying1,2; Peng, Jiale1; Li, Penghua1; Du, Haibo1; Li, Yaping1; Liu, Xingyong1; Zhang, Li1; Wang, Liang-Liang2; Zuo, Zhili1,2
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| 通讯作者 | Zhang, Li(zhangli19700554@163.com) ; Wang, Liang-Liang(wangliangliang@mail.kib.ac.cn) |
| 2019-04-01 | |
| 发表期刊 | COMPUTATIONAL BIOLOGY AND CHEMISTRY
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| ISSN | 1476-9271 |
| 卷号 | 79页码:165-176 |
| 摘要 | AMP-activated protein kinase (AMPK) plays a major role in maintaining cellular energy homeostasis by sensing and responding to AMP/ADP concentrations relative to ATP. AMPK has attracted widespread attention as a potential therapeutic target for metabolic diseases such as cancer and cardiovascular diseases. The structure-based 3D pharmacophore model was developed based on the training set. The best pharmacophore model Hypo5 was proposed and validated using a decoy set, an external test set. Hypo5, with the correlation coefficient value of 0.936, cost difference value of 112.08 and low RMS value of 1.63, includes a ionizable positive, a hydrogen bond donor, a hydrogen bond acceptor and two hydrophobic features, which showed a high goodness of fit and enrichment factor. Thus it was used as a 3D query to find potential activator from the SPECS Database. Then the ADMET descriptors were used to filter all of 158 screening molecules. The 41 filtering compounds were subsequently subjected to molecular docking and Quantitative structure activity relationship (QSAR) analysis. Finally, the compound H2 was picked out from those filtering compounds based on the receptor-ligand interaction analysis and the prediction of the QSAR models. And then it was submitted for molecular dynamics (MD) simulations to explore the stability of complex. The result indicates that the candidate could be considered a potential AMPK activator. |
| 关键词 | Pharmacophore modeling Molecular docking Quantitative structure activity relationship (QSAR) Molecular dynamics AMPK Activator |
| DOI | 10.1016/j.compbiolchem.2019.02.007 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000463124100019 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/67653 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 通讯作者 | Zhang, Li; Wang, Liang-Liang |
| 作者单位 | 1.Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong 643000, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yingying,Peng, Jiale,Li, Penghua,et al. Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study[J]. COMPUTATIONAL BIOLOGY AND CHEMISTRY,2019,79:165-176. |
| APA | Li, Yingying.,Peng, Jiale.,Li, Penghua.,Du, Haibo.,Li, Yaping.,...&Zuo, Zhili.(2019).Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study.COMPUTATIONAL BIOLOGY AND CHEMISTRY,79,165-176. |
| MLA | Li, Yingying,et al."Identification of potential AMPK activator by pharmacophore modeling, molecular docking and QSAR study".COMPUTATIONAL BIOLOGY AND CHEMISTRY 79(2019):165-176. |
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| Li-2019-Identificati（7335KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 浏览 下载 | |
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