Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation
文献类型：期刊论文
| 作者 | Chen, Li1; Zhao, Shuang1; Zhu, Yanyan1; Liu, Yongsheng1; Li, Huiyu1; Zhao, Qingjie2
|
| 刊名 | INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES
 |
| 出版日期 | 2021-06-17 |
| 页码 | 15 |
| 关键词 | STING Small molecule Binding site Modulated mechanism Molecular dynamics simulation pi-pi stacking interaction |
| ISSN号 | 1913-2751 |
| DOI | 10.1007/s12539-021-00446-3 |
| 通讯作者 | Li, Huiyu(huiyuli@shiep.edu.cn) ; Zhao, Qingjie(zhaoqingjie@simm.ac.cn) |
| 英文摘要 | Stimulator of interferon genes (STING), which is an integral ER-membrane protein, could induce an antiviral state and boost antitumor immunity. Recent experiments reported that different small molecules could modulate the conformation of the STING. However, the mechanism of small molecules modulating the conformation of STING is still unknown. To illustrate the conformational modulated mechanism of STING by small molecules at atomic level, we investigated the interactions between STING and the small molecules: cGAMP and diABZI with molecular dynamics (MD) simulations method. Interestingly, we found that the residues of STING in the binding pocket are more flexible in the monomers of STING than that in the dimer of STING. We also demonstrated that cGAMP and diABZI have a similar binding mode to STING monomers/dimer, and pi-pi stacking interactions play important roles for the agonists and STING. Our study proposed mechanistic insights into the STING conformation modulated by small molecules and we suggested that the special molecule (e. g. diABZI) could induce the conformational transition of STING from the "open" monomers to the "closed" dimer state. Our research may provide a clue for the development of cancer immunotherapy. |
| WOS关键词 | DEPENDENT ANTITUMOR IMMUNITY ; SWISS-MODEL REPOSITORY ; CGAMP ; PATHWAY ; RECOGNITION ; INHIBITION ; LIGAND ; ALGORITHMS ; ACTIVATION ; FEATURES |
| 资助项目 | Personalized Medicines-Molecular Signature-based Drug Discovery and Development |
| WOS研究方向 | Mathematical & Computational Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000662905700001 |
| 出版者 | SPRINGER HEIDELBERG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297175]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Huiyu; Zhao, Qingjie |
| 作者单位 | 1.Shanghai Univ Elect Power, Coll Math & Phys, Shanghai 200090, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Li,Zhao, Shuang,Zhu, Yanyan,et al. Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation[J]. INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES,2021:15. |
| APA | Chen, Li,Zhao, Shuang,Zhu, Yanyan,Liu, Yongsheng,Li, Huiyu,&Zhao, Qingjie.(2021).Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation.INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES,15. |
| MLA | Chen, Li,et al."Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation".INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES (2021):15. |
入库方式： OAI收割
来源：上海药物研究所
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