標題: 蛋白質結構模板之識別與搜尋
Identification and Search of Protein Structural Motif
作者: 郭育強
Kuo, Yu-Chiang
陳穎平
Chen, Ying-Ping
資訊科學與工程研究所
關鍵字: fastCOPS;BLAST;結構比對;區域保守性;結構模板搜尋;fastCOPS;BLAST;structural alignment;local conserved;structural motif search
公開日期: 2008
摘要: 在蛋白質科學領域裡,一般的認知是—胺基酸序列決定蛋白質結構,蛋白質結構決定蛋白質功能。隨著蛋白質結構數量的快速成長以及蛋白質體學技術的演進,許多研究胺基酸序列、蛋白質結構以及蛋白質功能之間關係的方法被不斷地提出。 本論文的研究是藉由檢討PROSITE 資料庫來探討胺基酸序列、蛋白質結構以及蛋白質功能三者之間的關係。PROSITE 是一個被廣泛應用,儲存完整的生物模板及其功能註解的資料庫。我們檢討PROSITE 蛋白質模板在結構面的保守性,藉以驗證蛋白質結構會導引蛋白質功能的基本信條。 我們發展了一套新的工具「fastCOPS」,其邏輯流程整合3D-BLAST 做為快速搜尋、MAMMOTH 做為精確結構比對方法,以及遞迴截取機制。一般來說,只要現行工具及方法能夠相容於fastCOPS 的設計,就能夠套用為架構元件。做為快速搜尋的元件,必須能夠接受一個蛋白質片段作為輸入;做為精確結構比對元件,必須具有比對部份結構並可適當插入間隔的功能。 我們應用了fastCOPS 做為蛋白質結構模板搜尋以及識別的工具。fastCOPS 利用許多的蛋白質結構模板做測試,包括treble clef finger 以及leucine-rich repeat。另外,我們亦利用了PROSITE 的蛋白質模板作為fastCOPS 輸入,來展示fastCOPS 能夠搜尋到在蛋白質結構方面具有保守性的相似片段,而若利用胺基酸序列搜尋方法卻是難以達成的能力。
In protein science, the common belief is that amino acid sequence determines protein structure, and then protein structure determines the biological function. As the availability of the rapidly growing number of protein crystal structures and the advent of proteomics technologies, many methods have been proposed to identify sequence-structure-function relationships. In this study, we investigate the relationship of protein sequence-structure-function by surveying PROSITE database. PROSITE is a widely used database that maintains annotated biological motifs. We review the structurally conserved property of PROSITE patterns to validate the fundamental principle-protein structure leads to protein function. In addition, we proposed fastCOPS that integrates a quick screening method, 3D-BLAST, an accurate structural alignment method, MAMMOTH, and the mechanism of recursive truncation with an appropriate logic flow. In general, tools and methods currently available can be adopted in the fastCOPS framework as long as they are compatible with the design. The quick component should be able to accept a protein fragment as input, and the accurate component has to be capable of aligning partial structures with possible gap insertions. We apply fastCOPS to achieve the task of structural motif search and identification. The fastCOPS has been evaluated on various structural motifs, including the treble clef finger motif, and the leucine-rich repeat motif. In addition, we use a PROSITE pattern as query to demonstrate the capability that fastCOPS can find structurally conserved fragments but using sequence alignment tool will hardly be achieved.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079655570
http://hdl.handle.net/11536/43375
Appears in Collections:Thesis


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