A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4
文献类型：期刊论文
| 作者 | Dai, Zi-Ru1,2; Ai, Chun-Zhi1; Ge, Guang-Bo1; He, Yu-Qi1; Wu, Jing-Jing1; Wang, Jia-Yue1; Man, Hui-Zi1; Jia, Yan1,2; Yang, Ling1 |
| 刊名 | international journal of molecular sciences
 |
| 出版日期 | 2015-07-01 |
| 卷号 | 16期号:7页码:14677-14694 |
| 关键词 | CYP3A4 steroids metabolic site mechanism-based prediction activation energy |
| 英文摘要 | early prediction of xenobiotic metabolism is essential for drug discovery and development. as the most important human drug-metabolizing enzyme, cytochrome p450 3a4 has a large active cavity and metabolizes a broad spectrum of substrates. the poor substrate specificity of cyp3a4 makes it a huge challenge to predict the metabolic site(s) on its substrates. this study aimed to develop a mechanism-based prediction model based on two key parameters, including the binding conformation and the reaction activity of ligands, which could reveal the process of real metabolic reaction(s) and the site(s) of modification. the newly established model was applied to predict the metabolic site(s) of steroids; a class of cyp3a4-preferred substrates. 38 steroids and 12 non-steroids were randomly divided into training and test sets. two major metabolic reactions, including aliphatic hydroxylation and n-dealkylation, were involved in this study. at least one of the top three predicted metabolic sites was validated by the experimental data. the overall accuracy for the training and test were 82.14% and 86.36%, respectively. in summary, a mechanism-based prediction model was established for the first time, which could be used to predict the metabolic site(s) of cyp3a4 on steroids with high predictive accuracy. |
| WOS标题词 | science & technology ; life sciences & biomedicine ; physical sciences |
| 类目[WOS] | biochemistry & molecular biology ; chemistry, multidisciplinary |
| 研究领域[WOS] | biochemistry & molecular biology ; chemistry |
| 关键词[WOS] | human liver-microsomes ; p450-mediated drug-metabolism ; phase-i metabolism ; active-site ; computational prediction ; crystal-structures ; p450 ; binding ; hydroxylation ; enzymes |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000359900100025 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/146469]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dai, Zi-Ru,Ai, Chun-Zhi,Ge, Guang-Bo,et al. A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4[J]. international journal of molecular sciences,2015,16(7):14677-14694. |
| APA | Dai, Zi-Ru.,Ai, Chun-Zhi.,Ge, Guang-Bo.,He, Yu-Qi.,Wu, Jing-Jing.,...&Yang, Ling.(2015).A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4.international journal of molecular sciences,16(7),14677-14694. |
| MLA | Dai, Zi-Ru,et al."A Mechanism-Based Model for the Prediction of the Metabolic Sites of Steroids Mediated by Cytochrome P450 3A4".international journal of molecular sciences 16.7(2015):14677-14694. |
入库方式： OAI收割
来源：大连化学物理研究所
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