改進RNA三級結構的多重比對

Abstract

近年來人們對非編碼RNA (ncRNAs) 的興趣正快速地成長，儘管這些ncRNAs不會被轉譯成蛋白質，但它們在細胞內卻扮演著許多重要的角色。事實上，大多數已有的ncRNAs的功能仍是未知並且是需要被預測的。從演化的角度而言，分子的結構往往會比它的序列來得保守些，因此，偵測出RNA三級結構之間的相似程度，將更能洞察出RNA分子的功能以及它們的演化關係，而這些功能與演化關係是無法單從RNA序列的資訊中給偵查出來的。因此，本研究的目的是設計出一個軟體工具可以有效率且正確地計算出多個RNA三級結構的相似程度。我們的方法是利用一個新的結構字元集將RNA三級結構轉成一級的結構字元式序列，然後再利用傳統的多重字元序列比對工具CLUSTAL W，以及新的類BLOSUM置換分數矩陣來比對出多重RNA結構字元式序列，進而推算出原RNA三級結構之間的相似程度。接著，我們利用上述的方法實做出一個軟體工具，稱之為iMARTS。最後我們利用一些RNA三級結構來測試iMARTS，並將其實驗結果與我們先前開發出來的軟體工具MARTS做比較，實驗的結果顯示出iMARTS確實比MARTS有更好的表現。因此，我們相信iMARTS在結構生物學的研究上可以做為一個有用的生物資訊工具。

Recently, there is a fast growing interest in noncoding RNAs (ncRNAs) because they play a lot of essential roles in many cellular processes, even though the transcripts of these ncRNAs are not translated into proteins. Actually, the function of most available ncRNAs is still unknown and needs to be determined. Since molecular structures are typically more evolutionarily conserved than sequences, detecting structural similarities among RNA three-dimensional (3D) structures can bring more significant insights into their functional and even evolutionary relationships that would not be detected by sequence information alone. Therefore, the purpose of this study is to design a software tool that can efficiently and accurately compute the structural similarity of multiple RNA 3D structures. Our method first uses a new structure alphabet to transform RNA 3D structures into 1D SA-encoded sequences and then uses a traditional multiple sequence alignment tool CLUSTAL W and a new BLOSUM-like scoring matrix to align the SA-encoded sequences of several RNAs for detecting the structural similarity of these RNAs. Next, we have implemented the above method into a software tool called iMARTS. Finally, we have tested iMARTS on some RNA 3D structures and compared its experimental results with those obtained by our previously developed tool MARTS. Consequently, the experimental results show that iMARTS indeed has a better performance when compared with MARTS. Therefore, we believe that iMARTS can serve as a useful tool in the study of structural biology.