改進結構字元式的RNA三級結構比對

Abstract

近年來我們越來越了解RNA分子，尤其是非編碼RNA，在細胞中的許多調節過程都扮演了非常重要的關鍵，譬如在轉錄後的調節、轉錄轉譯的基因調節、核醣體移碼與化學修飾等調節功能。如同蛋白質，RNA的功能也取決於它的三級結構並非其一級序列，這代表偵測RNA三級結構間的相似度能讓我們更深入的了解其功能甚至是演化上的關係。除此之外，近年來被解析出來的RNA結構不論是數量或是大小都快速的增加，使得我們若要使用人工的方式去比較或分析這些RNA的三級結構將會是困難且耗時的。因此，發展一個有效又準確去比較RNA三級結構的方法是相當重要的。 在這個研究中我們提出了一個改良結構字元式的RNA三級結構比對演算法。藉由採用兩個假扭轉角來取代四個真實的扭轉角與使用親合性互動式 (affinity propagation) 分群方法取代向量量子化 (vector quantization) 的分群方法來建構出新的結構字元集，這個新的結構字元集確實改善了先前研究中演算法的準確性。特別的是我們達成上述的改善時並沒有犧牲演算法的計算效率。除此之外我們也在實驗中證實了我們應用這個演算法所發展的程式工具iPARTS的確比起我們先前的版本PARTS有較好的表現，而PARTS已被證明是要比DIAL要有較好的準確性。因此，我們認為在結構生物學的研究上iPARTS可做為一個有用的工具，目前可連結到以下網址使用http://bioalgorithm .life.nctu.edu.tw/iPARTS/

In recent years, it is more and more clear that RNA molecules, especially the non-coding RNAs, play important roles in several regulatory processes, such as post-transcriptional regulation, transcriptional and translational gene regulation and chemical modification. Similar to proteins, the functions of these non-coding RNAs depend on their three-dimensional (3D) structures, rather than their primary sequences, suggesting that detecting structural similarities among RNA 3D structures can bring more significant insights into their functional and even evolutionary relationships. Moreover, the number and the size of solved RNA 3D structures have rapidly increased in past few years, making it difficult and time-consuming to manually compare and analyze these RNA 3D structures. Therefore, developing an effective and accurate method for RNA 3D structure comparison is imperative. In this study, we have proposed an improved structural alphabet-based algorithm for RNA 3D structure comparison. It improves the accuracy of our previous algorithm by replacing four standard torsion angles with two pseudotorsion angles and by using a recently introduced affinity propagation clustering approach for constructing of structural alphabet. Particularly, we achieve the above improvement without compromising the computational efficiency of the algorithm. We also demonstrate that the new version of the implemented program, called iPARTS, indeed outperforms its previous version, named PARTS, which in turn has been shown previously to outperform other existing tool DIAL. The iPARTS web server is available online at http://bioalgorithm .life.nctu.edu.tw/iPARTS/ that can serve as an useful tool in the study of structure biology.