Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening

doi:10.3390/biom11070929

	Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening
	Zhou, Qingtong 1; Guo, Wanjing 2,3; Dai, Antao 2,4; Cai, Xiaoqing 2,4; Vass, Marton 5; de Graaf, Chris 5; Shui, Wenqing6,7 ; Zhao, Suwen6,7 ; Yang, Dehua 2,3,4; Wang, Ming-Wei1,2,3,4,7
	2021-07
发表期刊	BIOMOLECULES (IF:4.8[JCR-2023],5.4[5-Year])
EISSN	2218-273X
卷号	11 期号:7
DOI	10.3390/biom11070929
摘要	Allosteric modulators have emerged with many potential pharmacological advantages as they do not compete the binding of agonist or antagonist to the orthosteric sites but ultimately affect downstream signaling. To identify allosteric modulators targeting an extra-helical binding site of the glucagon-like peptide-1 receptor (GLP-1R) within the membrane environment, the following two computational approaches were applied: structure-based virtual screening with consideration of lipid contacts and ligand-based virtual screening with the maintenance of specific allosteric pocket residue interactions. Verified by radiolabeled ligand binding and cAMP accumulation experiments, two negative allosteric modulators and seven positive allosteric modulators were discovered using structure-based and ligand-based virtual screening methods, respectively. The computational approach presented here could possibly be used to discover allosteric modulators of other G protein-coupled receptors.
关键词	GLP-1R virtual screening allosteric modulator drug discovery molecular docking
URL	查看原文
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000676655900001
出版者	MDPI
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127819
专题	iHuman研究所_PI研究组_水雯箐组生命科学与技术学院_特聘教授组_王明伟组 iHuman研究所_PI研究组_赵素文组
通讯作者	Zhao, Suwen; Yang, Dehua; Wang, Ming-Wei
作者单位	1.Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China; 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 5.Vrije Univ Amsterdam, Fac Sci, Amsterdam Inst Mol Med & Syst, Div Med Chem, NL-1081 Amsterdam, Netherlands; 6.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	iHuman研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Zhou, Qingtong,Guo, Wanjing,Dai, Antao,et al. Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening[J]. BIOMOLECULES,2021,11(7).
APA	Zhou, Qingtong.,Guo, Wanjing.,Dai, Antao.,Cai, Xiaoqing.,Vass, Marton.,...&Wang, Ming-Wei.(2021).Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening.BIOMOLECULES,11(7).
MLA	Zhou, Qingtong,et al."Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening".BIOMOLECULES 11.7(2021).