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
文献类型：期刊论文
| 作者 | 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
 |
| 出版日期 | 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 |
| WOS记录号 | WOS:000261711300014 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| URI标识 | http://www.irgrid.ac.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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来源：中国科学院大学
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