Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation

doi:10.1007/s12539-021-00446-3

	Molecular Dynamics Simulations Reveal the Modulated Mechanism of STING Conformation
	Chen, Li 1; Zhao, Shuang 1; Zhu, Yanyan 1; Liu, Yongsheng 1; Li, Huiyu 1; Zhao, Qingjie 2
刊名	INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES
	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.
资助项目	Personalized Medicines-Molecular Signature-based Drug Discovery and Development
WOS关键词	DEPENDENT ANTITUMOR IMMUNITY ; SWISS-MODEL REPOSITORY ; CGAMP ; PATHWAY ; RECOGNITION ; INHIBITION ; LIGAND ; ALGORITHMS ; ACTIVATION ; FEATURES
WOS研究方向	Mathematical & Computational Biology
语种	英语
出版者	SPRINGER HEIDELBERG
WOS记录号	WOS:000662905700001
内容类型	期刊论文
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.