Elastic network models and molecular dynamic simulations reveal the molecular basis of allosteric regulation in ubiquitin-specific protease 7 (USP7)
文献类型：期刊论文
| 作者 | Xu, Jing1; Wang, Yiran2,4; Zhang, Jiali1; Abdelmoneim, Amr Abbas1; Liang, Zhongjie3; Wang, Lei1; Jin, Jia1; Dai, Qi1; Ye, Fei1 |
| 刊名 | COMPUTERS IN BIOLOGY AND MEDICINE
 |
| 出版日期 | 2023-08-01 |
| 卷号 | 162页码:10 |
| ISSN号 | 0010-4825 |
| 关键词 | USP7 Allosteric regulation Elastic network models Molecular dynamics simulations |
| DOI | 10.1016/j.compbiomed.2023.107068 |
| 通讯作者 | Ye, Fei(yefei@zstu.edu.cn) |
| 英文摘要 | Ubiquitin-specific protease 7 (USP7) is one of the most abundant deubiquitinases and plays an important role in various malignant tumors. However, the molecular mechanisms underlying USP7's structures, dynamics, and biological significance are yet to be investigated. In this study, we constructed the full-length models of USP7 in both the extended and compact state, and applied elastic network models (ENM), molecular dynamics (MD) simulations, perturbation response scanning (PRS) analysis, residue interaction networks as well as allosteric pocket prediction to investigate allosteric dynamics in USP7. Our analysis of intrinsic and conformational dynamics revealed that the structural transition between the two states is characterized by global clamp motions, during which the catalytic domain (CD) and UBL4-5 domain exhibit strong negative correlations. The PRS analysis, combined with the analysis of disease mutations and post-translational modifications (PTMs) further highlighted the allosteric potential of the two domains. The residue interaction network based on MD simulations captured an allosteric communication path which starts at CD domain and ends at UBL4-5 domain. Moreover, we identified a pocket at the TRAF-CD interface as a high-potential allosteric site for USP7. Overall, our studies not only provide molecular insights into the conformational changes of USP7, but also aid in the design of allosteric modulators that target USP7. |
| WOS关键词 | DOMAIN ; PROTEINS ; CANCER ; DEUBIQUITINATION ; ACTIVATION ; USP7/HAUSP ; MECHANISM |
| 资助项目 | Zhejiang Province Natural Science Foun[Y23H300021] ; National Natural Science Foundation of China[81803339] |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics ; Computer Science ; Engineering ; Mathematical & Computational Biology |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:001016575600001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306382]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ye, Fei |
| 作者单位 | 1.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou 310018, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 3.Soochow Univ, Ctr Syst Biol, Sch Biol & Basic Med Sci, Dept Bioinformat, Suzhou 215123, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Jing,Wang, Yiran,Zhang, Jiali,et al. Elastic network models and molecular dynamic simulations reveal the molecular basis of allosteric regulation in ubiquitin-specific protease 7 (USP7)[J]. COMPUTERS IN BIOLOGY AND MEDICINE,2023,162:10. |
| APA | Xu, Jing.,Wang, Yiran.,Zhang, Jiali.,Abdelmoneim, Amr Abbas.,Liang, Zhongjie.,...&Ye, Fei.(2023).Elastic network models and molecular dynamic simulations reveal the molecular basis of allosteric regulation in ubiquitin-specific protease 7 (USP7).COMPUTERS IN BIOLOGY AND MEDICINE,162,10. |
| MLA | Xu, Jing,et al."Elastic network models and molecular dynamic simulations reveal the molecular basis of allosteric regulation in ubiquitin-specific protease 7 (USP7)".COMPUTERS IN BIOLOGY AND MEDICINE 162(2023):10. |
入库方式： OAI收割
来源：上海药物研究所
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