| 曾巧玲,刘鹰翔,李耿,马玉卓.化学通报,2021,84(5):486-496. |
| DCN1-UBE2M相互作用抑制剂的3D-QSAR、分子对接和分子动力学研究 |
| Study on 3D-QSAR, Molecular Docking and Molecular Dynamics of DCN1-UBE2M Interaction Inhibitor |
| 投稿时间：2020-10-08 修订日期：2020-11-10 |
| DOI： |
| 中文关键词: DCN1-UBE2M相互作用 哌啶基脲类化合物 3D-QSAR 分子对接 分子动力学模拟 |
| 英文关键词:DCN1-UBE2M interaction Piperidinylurea compounds 3D-QSAR Molecular docking Molecular dynamics simulation |
| 基金项目:国家自然科学基金项目（81803813）资助 |
|
| 摘要点击次数: 940 |
| 全文下载次数: 0 |
| 中文摘要: |
| 类泛素化是一种蛋白质翻译后修饰，其异常会导致神经退行性疾病和多种肿瘤的发生，因此它被视为有希望的抗肿瘤靶标。研究表明，抑制DCN1-UBE2M相互作用可选择性阻遏类泛素化。本文基于哌啶基脲类DCN1-UBE2M相互作用抑制剂进行3D-QSAR、分子对接和分子动力学模拟研究。利用3D-QSAR中的CoMFA和CoMSIA方法构建了相关模型，其交叉验证系数q2分别为0.686、0.682，拟合验证系数r2分别为0.966、0.931，表明模型是可靠的且预测能力较好。接着运用分子对接分析哌啶基脲类化合物与DCN1的相互作用，结果表明，它们主要通过氢键和疏水作用与靶蛋白结合。通过分子动力学模拟研究进一步了解结合模型和验证对接结果。本文所得的研究结果可为今后此类化合物的结构优化提供有效信息。 |
| 英文摘要: |
| Neddylation is a post-translational modification of protein, and its abnormality can lead to neurodegenerative diseases and a variety of tumors which is therefore regarded as a promising anti-tumor target. Blockage of DCN1-UBE2M interaction can selectively inhibit neddylation. In this paper, the study of 3D-QSAR, molecular docking and molecular dynamics simulation studies were carried out on the piperidinylurea DCN1-UBE2M interaction inhibitors. CoMFA and CoMSIA methods for 3D-QSAR were used to build the models, whose cross-validation coefficients q2 were 0.686 and 0.682, and the fitting verification coefficients r2 were 0.966 and 0.931, respectively, indicating the reliability of the model and its good predictive ability. Furthermore, molecular docking was used to analyze the interaction of piperidinylurea compounds with DCN1, and the results showed that they mainly bind to the target protein through hydrogen bond interaction and hydrophobic interaction. Study on molecular dynamics simulation further understand the binding model and verify the docking results. These research provided clues for structural optimization of such compounds. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |