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	The binding of thioflavin t and its neutral analog bta-1 to protofibrils of the alzheimer's disease a beta(16-22) peptide probed by molecular dynamics simulations
	Wu, Chun1,2; Wang, Zhixiang3; Lei, Hongxing4; Duan, Yong5,6; Bowers, Michael T.1,2; Shea, Joan-Emma1,2
刊名	Journal of molecular biology
	2008-12-19
卷号	384期号:3页码:718-729
关键词	Amyloid fibrils Alzheimer's disease a beta(16-22) peptide Aggregation Thioflavin t Molecular dynamics simulations
ISSN号	0022-2836
DOI	10.1016/j.jmb.2008.09.062
通讯作者	Shea, joan-emma(shea@chem.ucsb.edu)
英文摘要	Thioflavin t (tht) is a fluorescent dye commonly used to stain amyloid plaques, but the binding sites of this dye onto fibrils are poorly characterized. we present molecular dynamics simulations of the binding of tht and its neutral analog bta-1 [2-(4'-methylaminophenyl)benzothiazole] to model protofibrils of the alzheimer's disease a beta(16-22) (amyloid beta) peptide. our simulations reveal two binding modes located at the grooves of the beta-sheet surfaces and at the ends of the beta-sheet. these simulations provide new insight into recent experimental work and allow us to characterize the high-capacity, micromolar-affinity site seen in experiment as binding to the beta-sheet surface grooves and the low-capacity, nanomolar-affinity site seen as binding to the beta-sheet extremities of the fibril. the structure-activity relationship upon mutating charged tht to neutral bta-1 in terms of increased lipophilicity and binding affinity was studied, with calculated solvation free energies and binding energies found to be in qualitative agreement with the experimental measurements. (c) 2008 elsevier ltd. all rights reserved.
WOS关键词	AMYLOIDOGENIC HEXAPEPTIDE NFGAIL ; SOLID-STATE NMR ; DOCK-LOCK MECHANISM ; CONGO RED ; IMAGING AGENTS ; ORDERED OLIGOMERS ; EXPLICIT SOLVENT ; FORCE-FIELD ; BETA ; FIBRILS
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000261711300014
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2393297
专题	中国科学院大学
通讯作者	Shea, Joan-Emma
作者单位	1.Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA 2.Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA 3.Chinese Acad Sci, Coll Chem & Chem Engn, Grad Univ, Beijing, Peoples R China 4.Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China 5.Univ Calif Davis, UC Davis Genome Ctr, Davis, CA 95616 USA 6.Univ Calif Davis, Dept Appl Sci, Davis, CA 95616 USA
推荐引用方式 GB/T 7714	Wu, Chun,Wang, Zhixiang,Lei, Hongxing,et al. The binding of thioflavin t and its neutral analog bta-1 to protofibrils of the alzheimer's disease a beta(16-22) peptide probed by molecular dynamics simulations[J]. Journal of molecular biology,2008,384(3):718-729.
APA	Wu, Chun,Wang, Zhixiang,Lei, Hongxing,Duan, Yong,Bowers, Michael T.,&Shea, Joan-Emma.(2008).The binding of thioflavin t and its neutral analog bta-1 to protofibrils of the alzheimer's disease a beta(16-22) peptide probed by molecular dynamics simulations.Journal of molecular biology,384(3),718-729.
MLA	Wu, Chun,et al."The binding of thioflavin t and its neutral analog bta-1 to protofibrils of the alzheimer's disease a beta(16-22) peptide probed by molecular dynamics simulations".Journal of molecular biology 384.3(2008):718-729.

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