以球體為基礎擷取蛋白質內胺基酸3D結構資訊的研究

Abstract

蛋白質功能的表現上大多與結構有關，特別是在局部結構內部胺基酸相互的接觸(residue-residue contact)，更是直接與反應有密切的關係。胺基酸相互的反應作用已經被視為研究蛋白質摺疊與穩定性的重要過程，且蛋白質中胺基酸相互反應作用的型態十分多元，有效的在胺基酸相互的反應作用資訊上做探勘有助於不同觀點的議題，例如找出胺基酸的side-chain分群有助於蛋白質結構、功能與disordered regions之研究。有鑑於此本論文提供一個彈性且多維度的球體架構資料探勘方式，以達到探測不同型態胺基酸相互的反應作用現象，希望能有助於分析局部結構與此現象之間的關係。我們也發展出初步的網頁服務呈現出本論文球體架構。 在實驗部分，我們透過球體架構先觀察胺基酸本身周遭資訊，接著再進一步針對蛋白質與其它分子分析，包含蛋白質鏈結、DNA、RNA、het group等結構區域。在胺基酸本身的sidechain-sidechain interaction我們找出了相互作用頻率最高的前五組胺基酸與形成該現象的主要結構類型；在protein-protein interaction的結構主要集中在α-helix與α-helix這類型的胺基酸結構配對，我們也找出兩條鏈結反應下最長的重疊區段(overlapping segment)，並且也發現蛋白質1cwq、1e0p、1gu8、1gtv與1cm4含有特殊的鏈結重疊現象，而這些重疊現象的蛋白質鏈結記載著不同狀態下的生物特性；在protein-het group interaction 方面我們探測出一般蛋白質很容易與水形成反應作用，約有97%的作用與水有關係，而也發現較常與蛋白質鏈結發生反應的het group具有穩定結晶體的結構特性；protein-DNA interaction上我們發現Arginine與Lysine兩類胺基酸與DNA發生相互反應的比率較其它胺基酸高；我們也發現共有29條蛋白質鏈結存有同時與DNA、RNA有相互反應現象。觀察結果顯示，我們可以瞭解各種胺基酸反應的特性與其之間的關係，也給予我們對於廣域蛋白質與胺基酸周遭環境研究的完整觀察。

The structure of a protein is crucial to its function. In particular, the residue-residue contact on local structure was directly related to the protein function. Residue-residue contact was correlated with folding and stability of proteins. Mining the residue-residue contact can help scientist understand residue environmental information; for example, exploring the side-chain distribution can support the study of protein structure, protein function and disordered regions. In this work, our major contribution is to propose a multi-dimensional framework of sphere-based model to explore the residue environment, including to diverse residue-residue contacts. This framework also helps to analyze the relationship between local structure and residue-residue contacts. We also develop the prototype web service for demonstrating this framework. In experiment, the sphere-base framework was applied in the exploration of the information of the interaction between atoms, including complexed consisted of protein chain, DNA, RNA or heterogen atoms. In sidechain-sidechain interaction, we found the top five contacted residue pairs. In protein-protein interaction, the distribution of contacted structure was focus on the α-helix and α-helix pairs. We also comprehend the unusual overlapping on protein chains such as 1cwq, 1e0p, 1gu8, 1gtv and 1cm4. The overlapping proteins chain were record the combination of structure in different states of biological characteristics in PDB. In protein-het group interaction, we explored that 97% interaction contacted with H2O atoms, and top ranked het groups are chemical compounds used to stabilize structures for crystallization. In protein-DNA interaction, the arginine(R) and lysine(K) were preferred to contact with DNA nucleotides. We also explored that there were 29 protein chains contact with DNA and RNA nucleotides. According to observations we explored, we can comprehend the characteristics of diverse residue-residue contact and their relationship. These characteristics can give us a whole picture on residue environment of protein structures in Protein Data Bank.