Citation: Qiaoling Zeng, Yingxiang Liu, Geng Li, Yuzhuo Ma. Study on 3D-QSAR, Molecular Docking and Molecular Dynamics of DCN1-UBE2M Interaction Inhibitor[J]. Chemistry, ;2021, 84(5): 486-496. shu

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

1.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006
2.
College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006

Corresponding author: Yingxiang Liu, liuyingxiang@gzucm.edu.cn
Received Date: 8 October 2020
Accepted Date: 10 November 2020

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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.
- DCN1-UBE2M interaction,
- Piperidinylurea compounds,
- 3D-QSAR,
- Molecular docking,
- Molecular dynamics simulation
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