Computational Identification of a New Binding Site in Influenza Virus   Hemagglutinin for Membrane Fusion Inhibitors

doi:10.1111/cbdd.12156

CORC > 北京大学 > 化学与分子工程学院

	Computational Identification of a New Binding Site in Influenza Virus Hemagglutinin for Membrane Fusion Inhibitors
	Sun, Lidan ; Tian, Feng ; Feng, Baosheng ; Liu, Zhenming ; Zhang, Liangren ; Pei, Jianfeng
刊名	chemical biology drug design
	2013
关键词	binding site drug resistance hemagglutinin influenza virus membrane fusion inhibitors A VIRUS VIRAL FUSION DESIGN DERIVATIVES RESISTANCE MECHANISM PROTEINS ORIGIN ENTRY PH
DOI	10.1111/cbdd.12156
英文摘要	The influenza virus hemagglutinin is a potential drug target for antivirus treatment. A variety of membrane fusion inhibitors targeting hemagglutinin have been discovered, but the binding sites and modes, important for understanding membrane fusion and rational drug design, have not yet been elucidated. In this article, we investigated the possible hemagglutinin binding sites for the current membrane fusion inhibitors. Four possible binding pockets (Pocket A, B, C, and D) at the stalk region of hemagglutinin were detected and defined using the CAVITY program. Most of the current membrane fusion inhibitors were reported to bind to Pocket C by amino acid mutation experiments and molecular modeling simulation. However, our binding site prediction suggested that Pocket A is the best ligand binding site other than Pocket C. Using a specific computational protocol combining molecular docking, three-dimensional QSAR, and receptor mimicking, we further found that Pocket A is the putative binding site for a series of membrane fusion inhibitors (1-phenyl-cycloalkane carbamides). This is further proven by the antiviral spectrum of the inhibitors. This protocol for the identification of ligand binding sites in influenza hemagglutinin is also applicable for the analysis of other protein targets with no explicit binding information.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000323376300004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; Chemistry, Medicinal; SCI(E); PubMed; 0; ARTICLE; 3; 267-274; 82
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/156445]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Sun, Lidan,Tian, Feng,Feng, Baosheng,et al. Computational Identification of a New Binding Site in Influenza Virus Hemagglutinin for Membrane Fusion Inhibitors[J]. chemical biology drug design,2013.
APA	Sun, Lidan,Tian, Feng,Feng, Baosheng,Liu, Zhenming,Zhang, Liangren,&Pei, Jianfeng.(2013).Computational Identification of a New Binding Site in Influenza Virus Hemagglutinin for Membrane Fusion Inhibitors.chemical biology drug design.
MLA	Sun, Lidan,et al."Computational Identification of a New Binding Site in Influenza Virus Hemagglutinin for Membrane Fusion Inhibitors".chemical biology drug design (2013).