| Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction | |
Liu X(刘鑫) ; Zhao YP(赵亚溥); Zhao YP(赵亚溥)
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| Source Publication | PLoS One
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| 2010 | |
| Volume | 5Issue:1Pages:e8441 |
| ISSN | 1932-6203 |
| Abstract | Many diseases are believed to be related to abnormal protein folding. In the first step of such pathogenic structural changes, misfolding occurs in regions important for the stability of the native structure. This destabilizes the normal protein conformation, while exposing the previously hidden aggregation-prone regions, leading to subsequent errors in the folding pathway. Sites involved in this first stage can be deemed switch regions of the protein, and can represent perfect binding targets for drugs to block the abnormal folding pathway and prevent pathogenic conformational changes. In this study, a prediction algorithm for the switch regions responsible for the start of pathogenic structural changes is introduced. With an accuracy of 94%, this algorithm can successfully find short segments covering sites significant in triggering conformational diseases (CDs) and is the first that can predict switch regions for various CDs. To illustrate its effectiveness in dealing with urgent public health problems, the reason of the increased pathogenicity of H5N1 influenza virus is analyzed; the mechanisms of the pandemic swine-origin 2009 A(H1N1) influenza virus in overcoming species barriers and in infecting large number of potential patients are also suggested. It is shown that the algorithm is a potential tool useful in the study of the pathology of CDs because: (1) it can identify the origin of pathogenic structural conversion with high sensitivity and specificity, and (2) it provides an ideal target for clinical treatment. |
| Subject Area | 生物力学 |
| DOI | 10.1371/journal.pone.0008441 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:000278099200002 |
| WOS Keyword | VIRUS NUCLEOPROTEIN GENE; AMYLOID FIBRILS; INFLUENZA-VIRUS; PARKINSONS-DISEASE; SYNTHETIC PEPTIDES; ALPHA-SYNUCLEIN; PRION PROTEIN; IN-VITRO; MUTATIONS; VARIANT |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/33081 |
| Collection | 非线性力学国家重点实验室 |
| Corresponding Author | Zhao YP(赵亚溥) |
| Recommended Citation GB/T 7714 | Liu X,Zhao YP,Zhao YP. Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction[J]. PLoS One,2010,5,1,:e8441. |
| APA | Liu X,Zhao YP,&赵亚溥.(2010).Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction.PLoS One,5(1),e8441. |
| MLA | Liu X,et al."Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction".PLoS One 5.1(2010):e8441. |
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| journal[1].pone.0008（670KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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