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研究生： 葉俊霆
Chun-ting Yeh
論文名稱： DS-SARST : 利用Ramachandran序列轉換法協助搜尋蛋白質結構之區域交換現象
指導教授： 呂平江
Ping-Chiang Lyu
口試委員:
學位類別： 碩士
Master
系所名稱： 生命科學暨醫學院 - 生物資訊與結構生物研究所
Institute of Bioinformatics and Structural Biology
論文出版年： 2008
畢業學年度： 96
語文別： 英文
論文頁數： 70
中文關鍵詞： 結構比對 、蛋白質搜尋工具 、蛋白質三級結構交換 、蛋白質結構變化 、蛋白質四級結構
外文關鍵詞： Structure alignment, protein search tool, 3D domain swapping, conformational change, Protein quaternary structure, PDB
相關次數： 點閱：2  下載：0 
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    • Three-dimensional (3D) domain swapping is a mechanism for forming protein quaternary structures from their monomers. It is defined as two or more protein chains exchanging part of their identical structure domain to form intertwined dimer or higher oligomers. 3D domain swapping is considered that it can occur under appropriate conditions in any protein with an unconstrained terminus. The term “3D domain swapping” was first used to describe the dimeric structure of diphtheria toxin in 1994. After that, the data of domain-swapped proteins has greatly expanded.
    Because sequence comparison has shown that 3D domain-swapped partners often share minor sequence similarity and traditional rigid structural comparison methods, such as CE (Combinatorial Extension) and DALI (Distance Matrix Alignment), are too rigid in nature to identify their real structural similarities, it is difficult to detect 3D domain swapping from protein structure databases. Here we present DS-SARST (3D Domain Swapping Search Aided by Ramachandran Sequential Transformation) to be an efficient database search tool.
    DS-SARST utilizes the linear encoding algorithm RST to transform 3D protein structures into one-dimensional (1D) structural strings, the flexible properties of which in describing backbone conformations can be applied to the rapid detection of 3D domain swapping. Furthermore, we use a “double filter-and-refine” strategy to improve its accuracy. We suppose that DS-SARST can be an efficient structural database search tool useful in detecting 3D domain swapping cases and offering sufficient clues for their evolutionary relationships.

    3D domain swapping 是一種蛋白質由自身三級結構交互作用而產生四級結構的機制，它可以被看作是兩個蛋白質結構彼此交換相同的區域而形成了彼此糾結的同質聚合物。
    一般認為，只要蛋白質具有未被束縛之末端且條件合適，即可能發生3D domain swapping 之現象。
    3D domain swapping首度被提出為一種蛋白質演化機制是在西元1994年，時至今日人們所解出結構的此種蛋白已增加了不少。
    從目前的研究得知，3D domain swapping與演化上的蛋白質功能強化及蛋白質錯誤堆積沉澱疾病有關：如狂牛症、老人癡呆症等。越來越多學者思考著其結合過程與演化機制並嘗試找出其規律性以及人為的可能性。但礙於缺乏大量整合性資料，前人的研究通常都只在特定幾個例子上做討論。
    由於3D domain swapping的蛋白質間常常彼此的序列相似度不高，無法單純使用序列比對；而傳統的結構比對在比對3D domain swapping上往往無法完整地偵測到正確的結構相似程度，本研究報告提出一種新的演算方法 — DS-SARST (利用 Ramachandran 序列轉換法協助搜尋蛋白質結構之區域交換現象)。DS-SARST利用RST線性編碼演算法，將蛋白質的3D結構轉變成1D的字串，利用這種有結構意義的字串來進行具有彈性且快速的搜尋比對。DS-SARST能夠從已有的蛋白質結構資料庫中，取出資料並偵測其3D domain swapping 現象。此外，利用DS-SARST，我們可以建立3D domain-swapping資料庫，有助人們對這類現象做進一步研究。

    Abstract 5 中文摘要 6 Abbreviations 7 Chapter 1. Introduction 8 1.1 3D domain swapping 8 1.2 Review of protein structure comparisons 9 1.3 Motivation and purpose 10 1.4 Overview of DS-SARST 12 Chapter 2. Materials 13 2.1 Hardware 13 2.2 Software 13 2.3 Databases 14 2.3.1 PDB database 14 2.3.2 PQS database 14 2.3.3 PDB_Select database 15 2.4 Search engine 15 Chapter 3. Methods 17 3.1 Preparation of training and testing sets 17 3.2 The double-filter-and-refine-stage 18 3.2.1 Screening stage 19 3.2.2 Refinement stage 19 3.2.2.1 Flexible structure alignment 19 3.2.2.2 Rigid structure alignment 20 3.2.2.3 Alternative structure alignment 20 3.2.3 Parameters 21 3.3 DS-score 22 3.4 Hinge loop detection 23 Chapter 4. Results and Discussions 24 4.1 Optimization of parameter settings 24 4.2 Experiments on published DS pairs 27 4.3 Experiments on the testing set 29 4.4 Speed evaluation 30 4.5 On DS-score 30 4.6 Representative database search of 3D domain swapping 31 4.7 Hinge loop detection 32 4.8 Implementation of DS-SARST web service 33 Chapter 5. Conclusion 34 References 35

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