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論文名稱(外文):A database of protein conformational changes upon interactions
指導教授(外文):Tien-Hao Chang
外文關鍵詞:protein structureconformational transition
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蛋白質在很多生物機制裡扮演著重要的角色,這些生物機制是由一連串的蛋白質跟各式各樣的生物分子之間的反應所導致。在反應過程中許多蛋白質被觀察到會有結構上的轉變(conformational transitions),且在這些有結構轉變之處往往是反應過程中最關鍵的位置。因此,收集與分析蛋白質反應前後的結構對將有助於了解這些生物機制。
本研究的目的是發展一個收集蛋白質的結合前結構(apo structure)與結合後結構(holo structure)的資料庫。之前的許多研究藉由收集蛋白質反應前後的結構,來分析蛋白質在反應過程中結構的轉變與會影響蛋白質生物機能的重要胺基酸。然而各種不同的研究對於這種反應前後結構對(structure pairs)的收集程序通常不一致,導致彼此的資料無法互相使用。所以本研究提供一個簡單和統一的系統讓使用者能輕鬆取得這些資料。
我們經由分析存放在Protein Data Bank(PDB)裡超過七萬筆的結構檔,整理超過七十萬組的蛋白質結構對,與現有同類型最大的資料庫相比之下,多出將近30倍。並且提供一個互動式3D裝置讓使用者可以快速看到蛋白質反應前後的結構相互疊置在一起,幫助觀察其結構差異變化。
Proteins play important roles in many biological processes. These biological processes are conducted by a series of protein interactions with various biological molecules. These interactions are commonly observed to contain conformational transitions. Furthermore, the regions that undergo conformational transitions are usually the most critical positions in the interaction. Therefore, to collect and analyze protein structures before and after interaction helps to understand these biological processes.
This work aims at developing a database of protein structures before (apo) and after binding (holo). Many studies collected apo–holo structure pairs to investigate the conformational transitions and critical residues. However, the collection process usually varies from study to study and the data cannot be reused. This database is designed to provide an easy and unified system for users to access this data.
By analyzing more than 70,000 entries collected in the Protein Data Bank (PDB), we compiled more than 700,000 apo–holo pairs, which is about 30 times larger than the second largest collection of similar data. In addition, the proposed database includes an interactive 3D interface for users to quickly see the apo and holo structures superimposed in space, which helps to explore conformational transitions from apo structures to the corresponding holo structures.
致謝 7
目錄 8
圖目錄 10
表目錄 12
第 一 章 緒論 1
第 二 章 相關研究 3
2.1生物體內的主要分子種類 3
2.1.1蛋白質 3
2.1.2去氧核糖核酸-DNA 4
2.1.3配體-ligand 6
2.1.4離子-ion 7
2.2結構變化的類型 8
2.2.1非穩定和穩定區結構互相的轉變 8
2.2.2二級結構的轉變 9
2.3 相關資料庫 10
2.3.1 Protein Data Bank(PDB)10
2.3.3 Swiss-Prot 10
2.3.4 PDBsum 11
2.3.5 Comsin 11
第 三 章 資料收集、方法與分析 13
3.1分子對映 13
3.2結合前後結構對 17
3.3胺基酸序列對映 20
3.4結合前後的結構轉變 24
3.5結構的疊置演算法 26
3.6分析 27
3.6.2主要物種分佈 28
3.6.3依據不同的添加物類型作分析 29
3.6.4蛋白質結合前複合物數量與添加物分子的數量分析 30
第 四 章 使用介面、網站個案分析與資料庫比較 33
4.1使用者介面 33
4.1.1首頁 34
4.1.2結果頁 36
4.1.3 結構序列頁 37
4.2個案分析 40
4.3資料庫比較 41
4.4網站的流量統計 44
第 五 章 結論與未來展望 45
5.1結論 45
5.2未來展望 45
參考文獻 46

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