DCN1-UBE2M相互作用抑制剂的3D-QSAR、分子对接和分子动力学研究

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...

Study on 3D-QSAR, Molecular Docking and Molecular Dynamics of DCN1-UBE2M Interaction Inhibitor

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, 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 reliability and 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. Molecular dynamics simulation studies further understand the binding model and verify the docking results. These research provided clues for structural optimization of such compounds.