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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 周佳靚(Chia-Ching Chou) | |
| dc.contributor.author | Chien-Yu Pan | en |
| dc.contributor.author | 潘建宇 | zh_TW |
| dc.date.accessioned | 2022-11-23T09:23:38Z | - |
| dc.date.available | 2021-07-23 | |
| dc.date.available | 2022-11-23T09:23:38Z | - |
| dc.date.copyright | 2021-07-23 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-07-16 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80058 | - |
| dc.description.abstract | 上皮角蛋白是一種中間絲蛋白。它是維持人體最大器官皮膚表皮中細胞核穩定性的關鍵因素之一。它會吸收水分並承受外部壓力，從而影響皮膚的結構穩定性和機械性能。人的皮膚角蛋白由I型和II型角蛋白組成，通過鏈內氫鍵和鏈間的疏水作用能穩定地形成螺旋狀捲曲螺旋結構。K5/K14為本研究所探討的一種上皮角蛋白，關於此角蛋白的序列變異導致的遺傳疾病為遺傳性表皮分解水泡症，為普遍被大眾知道的泡泡龍疾病。根據文獻提出的角蛋白中間絲的組裝模型，在上皮角蛋白的結構之1B-1B區域之間旋鈕-口袋(Knob-Pocket)的交互作用會影響水平方向的組裝。另一方面發現在2B-2B結構域之間的ID1 接觸與中間絲的延長有關。目前X射線衍射實驗無法獲得全長中間絲的結構，因此不能全盤了解中間絲的組裝方式。本研究通過已知的蛋白質序列構建了完整的人體上皮角蛋白，應用全原子模型建構出角蛋白中間絲的模型並透過分子動力學模擬討論在1B以及2B結構域中二聚體及四聚體間的結構和氫鍵關係，以及透過拉伸分子動力學模擬獲得其力學特性，並且討論不同點位的錯義基因突變與其角蛋白組裝力學性質之間的相關性。我們發現在序列上不同位置的點突變會以不同方式影響1B區域的截斷四聚體結構，而對於2B區域相同位置的點突變並不一定影響異二聚體的結構，反之導致在四聚體的組裝差異。最後我們的結果與最新的實驗觀察結果進行進一步比較，連結基因造成的結構缺陷在分子尺寸上對於整體角蛋白中間絲的組裝情形以及力學性質的影響。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T09:23:38Z (GMT). No. of bitstreams: 1 U0001-1407202112101900.pdf: 6479913 bytes, checksum: 23c03813af9e86eb55db176e19b1b73d (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書 # 誌謝 i 中文摘要 ii ABSTRACT iii 目錄 v 圖目錄 viii 表目錄 xi 第一章 緒論 1 1.1 研究動機與目的 1 1.2 角蛋白中間絲文獻回顧 3 1.3 角蛋白中間絲 6 1.4 螺旋二級結構與卷曲螺旋 11 1.5 論文架構 14 第二章 研究方法 15 2.1 分子動力學模擬方法 15 2.1.1 勢能函數 15 2.1.2 系綜 16 2.1.3 Langevin Dynamic and Lavgevin piston Nosé–Hoover method 16 2.1.4 韋爾萊積分法 17 2.1.5 粒子網格埃瓦爾德方法 18 2.1.6 週期性邊界、截斷半徑及韋爾萊表列法 20 2.1.7 分子動力學模擬流程 22 2.2 拉伸分子動力學方法 23 2.3 胺基酸作用傾向評分矩陣 26 2.4 蛋白質相似性度量 28 2.5 本研究之模擬參數設定以及分析方法 29 2.5.1 模擬參數設定 29 2.5.2 RMSF、Length、D-spacing以及卷曲角度之計算 29 第三章 角蛋白模型建構 31 3.1 七肽重複以及卷曲螺旋預測 31 3.2 K5/K14全長角蛋白模型 34 第四章 K5/K14角蛋白1B結構域模擬結果 37 4.1 角蛋白1B結構域二聚體模擬結果 37 4.2 角蛋白1B結構域四聚體模擬結果 39 4.3 角蛋白四聚體力學分析 48 第五章 K5/K14角蛋白2B結構域模擬結果 56 5.1 K5/K14角蛋白2B結構域模擬結果 59 5.2 二聚體結構分析 61 5.3 四聚體組裝分析 64 5.4 四聚體力學性質探討 74 5.5 拉伸過程能量變化討論 81 第六章 結論及未來展望 83 6.1 結論 83 6.2 未來展望 85 參考文獻 86 附錄一：WT、L311R、R265P氫鍵以及接觸分布表。 91 附錄二：WT case I與實驗ID1 接觸的結構比較表。 94 附錄三：ID1 接觸三個胺基酸對之距離表。 96 附錄四：2B四聚體各個案例的氫鍵機率分布圖。 98 附錄五：2B結構域拉伸過程的二級結構變化圖。 99 | |
| dc.language.iso | zh-TW | |
| dc.subject | 遺傳性表皮分解水泡症 | zh_TW |
| dc.subject | 上皮角蛋白 | zh_TW |
| dc.subject | 分子動力學 | zh_TW |
| dc.subject | 中間絲 | zh_TW |
| dc.subject | 卷曲螺旋 | zh_TW |
| dc.subject | 旋鈕-口袋 | zh_TW |
| dc.subject | Molecular dynamics | en |
| dc.subject | Knob-pocket | en |
| dc.subject | Epidermolysis bullosa simplex | en |
| dc.subject | Coiled-coil | en |
| dc.subject | Intermediated filament | en |
| dc.subject | Epithelial keratin | en |
| dc.title | 以分子動力學模擬探討上皮角蛋白K5/K14之分子結構組裝及力學性質 | zh_TW |
| dc.title | Molecular Structure and Nanomechanical Properties of Human Epithelial Keratin K5/K14 Using Atomistic Simulation | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李世光(Hsin-Tsai Liu),許聿翔(Chih-Yang Tseng),陳志鴻 | |
| dc.subject.keyword | 上皮角蛋白,分子動力學,中間絲,卷曲螺旋,旋鈕-口袋,遺傳性表皮分解水泡症, | zh_TW |
| dc.subject.keyword | Epithelial keratin,Molecular dynamics,Intermediated filament,Coiled-coil,Epidermolysis bullosa simplex,Knob-pocket, | en |
| dc.relation.page | 100 | |
| dc.identifier.doi | 10.6342/NTU202101458 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-07-19 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 應用力學研究所 | zh_TW |
| Appears in Collections: | 應用力學研究所 | |
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| File | Size | Format | |
|---|---|---|---|
| U0001-1407202112101900.pdf | 6.33 MB | Adobe PDF | View/Open |
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