| DC 欄位 |
值 |
語言 |
| DC.contributor | 化學學系 | zh_TW |
| DC.creator | 曾勝煊 | zh_TW |
| DC.creator | Sheng-Xuan Zeng | en_US |
| dc.date.accessioned | 2009-10-15T07:39:07Z | |
| dc.date.available | 2009-10-15T07:39:07Z | |
| dc.date.issued | 2009 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:88/thesis/view_etd.asp?URN=962203034 | |
| dc.contributor.department | 化學學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | 本論文利用平行淬煉分子動態法 (Replica-Exchange molecular dynamics, REMD) 模擬類澱粉蛋白(Aβ)片段- Aβ25-35及其突變物N27A- Aβ25-35折疊及穿膜的機制。Aβ是阿茲海默症的主要病源，Aβ25-35保有和全長A???????類似的特性?具細胞毒性及amphipathicity (N?端具親水性，C?端具疏水性)。模擬中，Aβ25-35是以全原子的方式進行，水相及膜是以implicit model的方式進行，搭配REMD，以達到有效率的空間搜尋效果。
模擬結果顯示，Aβ25-35以疏水性的C?端插入膜的疏水區域，並形成穩定的α-helix構形 (Ala30- Leu34); N?端(Gly25 -Lys28)具極性，分佈在水相及頭基的區域，沒有明顯的二級結構; 結果和NMR決定的結構吻合。此外有一小部份的Aβ25-35越過了能量障礙深入膜的疏水核心區域，但並不是穩定結構。
N27A-Aβ25-35 是將Aβ25-35中極性的Asn取代成疏水性Ala，此一改變使得N27A-Aβ25-35毒性下降。模擬結果顯示，N27A-Aβ25-35 和Aβ25-35具有相似的構形及性質，但N27A-Aβ25-35 的C?端較Aβ25-35更深入膜的疏水區域，α-helix構形往N?端延長且較穩定。
膜變薄效應也會影響Aβ25-35及N27A-Aβ25-35的構形，當膜逐漸變薄時，Aβ25-35及N27A-Aβ25-35會更容易深入膜內，形成較長且穩定的α-helix構形。
| zh_TW |
| dc.description.abstract | The folding and membrane insertion of the Alzheimer’s amyloid-β(25-35) peptide and the mutate N27A-Aβ(25-35) peptide are explored using replica exchange molecular dynamics(REMD). All the peptide use all atom model and the solvent region (water and water-membrane region) are implicit solvent model This amphiphilic peptide (hydrophilicity in N-terminus , hydrophobicity in C-terminus) is a natural by-product of the Alzheimer’s amyloid-β(1-40) peptide and retains the toxicity of its full-length counterpart as the ability to aggregate into β-sheet rich fibrils.
The simulation result show that Aβ(25-35) insert into the membrane and form the helix structure in C-terminus (Ala30-Leu34);and N-terminus(Gly25-Lys28) are disordered at the water region.Our simulation result agree with the NMR structure.A little portion of structures inser into membrane but the structures are unstable.
N27A-Aβ(25-35) peptide,where Asn27 is repliced by Ala. The mutate peptide shows lower neurotoxicity than the wild type despite its increased hydrophobicity. The simulation result shows N27A-Aβ(25-35) peptide and Aβ(25-35) peptide have similar structure and property, but N27A-Aβ(25-35) peptide can insert into membrane more deeper than Aβ(25-35) and the helix structure form more complete than Aβ(25-35).The membrane thining effect also affect the structure of Aβ(25-35) and N27A-Aβ(25-35). When the membrane become thin,two kind of peptide can insert into membrane easily and form stable α-helix structure.
| en_US |
| DC.subject | 分子動態模擬 | zh_TW |
| DC.subject | 類澱粉蛋白 | zh_TW |
| DC.subject | 阿茲海默症 | zh_TW |
| DC.subject | molecular dynamics simulation | en_US |
| DC.subject | amyloid beta | en_US |
| DC.subject | Alzheimer's disease | en_US |
| DC.title | Replica-Exchange分子動態模擬法研究類澱粉胜肽25-35
嵌入膜與折疊的行為 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | Folding and Membrane Insertion of Amyloid-β Peptide (25-35): A Replica-Exchange Molecular Dynamics Simulation Study
| en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |