Molecular dynamics simulations reveal the mechanism of the interactions between the inhibitors and SIRT2 at atom level

doi:10.1080/08927022.2020.1757093

	Molecular dynamics simulations reveal the mechanism of the interactions between the inhibitors and SIRT2 at atom level
	Wang, Xiaoyu 1,2; Song, Menghua 1; Zhao, Shuang 1; Li, Huiyu 1; Zhao, Qingjie 2; Shen, Jingshan 2
刊名	MOLECULAR SIMULATION
	2020-05-23
卷号	46 期号:8 页码:638-649
关键词	SIRT2 inhibitor molecular dynamics simulation TCMs hydrophobic and pi-pi interactions
ISSN号	0892-7022
DOI	10.1080/08927022.2020.1757093
通讯作者	Li, Huiyu(huiyuli@shiep.edu.cn) ; Zhao, Qingjie(zhaoqingjie@simm.ac.cn)
英文摘要	The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a close role in cancers. Exploring the proper inhibitors for SIRT2 has attracted great interest in the experiment. However, the detail of the interaction mechanisms between inhibitors and SIRT2 is not well understood. In our study, we synthesised SIRT2 selective inhibitor TPN0_C7 as a model of the proper inhibitor of SIRT2. With the molecular dynamics (MD) simulations, we found that the hydrophobic interactions play the important roles between the inhibitors and SIRT2. According to the conformation character of the inhibitor TPN0_C7, we also explored the natural product, Ge Gen (Puerarol is one of the components.), which is a very effective herb for cancer described in Traditional Chinese Medicine (TCMs) library. Dramatically, we found that the structurally similar inhibitors, Puerarol and TPN0_C7, have the similar binding sites on SIRT2. The hydrophobic and pi-pi interactions between inhibitors and SIRT2 are important during the progress of the dynamic simulations. In summary, our study uncovers the interaction mechanisms between the inhibitors and SIRT2 at atom level, which may provide clues to explore more proper inhibitors from TCMs.
资助项目	`Personalized Medicines -Molecular Signature-based Drug Discovery and Development', Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040322]
WOS关键词	TRADITIONAL CHINESE MEDICINE ; STRUCTURAL BASIS ; CELL-DEATH ; CANCER ; DEACETYLASE ; DISCOVERY ; SELECTIVITY ; CARCINOMA ; APOPTOSIS ; SIRTUINS
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000532064700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280387]
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, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaoyu,Song, Menghua,Zhao, Shuang,et al. Molecular dynamics simulations reveal the mechanism of the interactions between the inhibitors and SIRT2 at atom level[J]. MOLECULAR SIMULATION,2020,46(8):638-649.
APA	Wang, Xiaoyu,Song, Menghua,Zhao, Shuang,Li, Huiyu,Zhao, Qingjie,&Shen, Jingshan.(2020).Molecular dynamics simulations reveal the mechanism of the interactions between the inhibitors and SIRT2 at atom level.MOLECULAR SIMULATION,46(8),638-649.
MLA	Wang, Xiaoyu,et al."Molecular dynamics simulations reveal the mechanism of the interactions between the inhibitors and SIRT2 at atom level".MOLECULAR SIMULATION 46.8(2020):638-649.