| DC 欄位 |
值 |
語言 |
| DC.contributor | 物理學系 | zh_TW |
| DC.creator | 周俐君 | zh_TW |
| DC.creator | Li-jun Chou | en_US |
| dc.date.accessioned | 2007-7-23T07:39:07Z | |
| dc.date.available | 2007-7-23T07:39:07Z | |
| dc.date.issued | 2007 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:88/thesis/view_etd.asp?URN=93222023 | |
| dc.contributor.department | 物理學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | 腦內神經組織中的普恩蛋白，當其發生錯誤摺疊並且誘發相同蛋白發生病變而成為類澱粉沉澱時將引發神經退化性疾病，例如，庫賈式症（Creutzfeldt-Jakob(CJD )）、狂牛症（Bovine Spongiform Encephalopathy (BSE )）、羊搔癢症（Scrapie）。有數種理論模型嘗試解釋此纖維化的發生機制。其中模板輔助理論認為有一模板存在使得普恩蛋白的基態PrPC 被誘發成為PrPSc，其氨基酸序列一
致但本來富含α-螺旋的普恩蛋白變成β-版。本研究工作旨在探討病發初期利用生物資訊法所預測最有可能的富含β-版 PrPSc 結構，是如何影響PrPC 的H1 螺旋的穩定性並驗證模板輔助模型。我們設計了兩系列電腦模擬實驗。實驗發現在150 奈秒的分子動力學模擬時間內含有部分解構的H1 螺旋結構的PrPC在類PrPSc的影響下H1 螺旋結構重新摺疊為α螺旋且更加穩定同時也顯示了兩穩定的新髮夾構形的形成。然而此二髮夾構形在H1 未部分解構的PrPC 並未形成. 這或許說明了病變初期H1 的部分解構是必經的一個過程。 | zh_TW |
| dc.description.abstract | Prion misfolding induces neurodegenerative disease, such as Cretzfeldt-Jakob (CJD), Bovine Spongiform Encephalopathy (BSE), Scrapie. A morbid state of prion will induce normal prion misfolding and gather themselves into fiber.
There are few theoretical models which explain how the normal protein unfold and fold into morbid state. One of machine model, template-assistance model, thinks that the existence of template prion, PrPSc will induce unfolding of normal prion PrPC with the same amino acid sequence but different structures (PrPSc is full of βstrand). Up to now, we have not known the accurate structure of PrPSc.
We use biological information to predict possible structure of PrPSc and study how PrPSc affects H1 of prion and verify template-assistance model. We design two series two experiments. We find out that the states of unfolding H1 near with PrPSc will refold into stable αhelix. Besides, there are two β hairpin like form. It may be thought that unfold H1 is middle state of PrPSc. | en_US |
| DC.subject | 普恩 | zh_TW |
| DC.subject | Prion | en_US |
| DC.title | 普恩蛋白發病機制的分子動力學模擬研究 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | Mechanisms of Prion disease revealed by molecular dynamic simulations | en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |