在生物學上RNA 是非常重要的分子，因為它在細胞中具有多種調節功能。基本上，RNA的功能大都取決於它的三級結構。因此，發展出能夠有效率且準確地比較出兩個RNA結構之間相似程度的工具將可以幫助生物學家更深入瞭解RNA的功能與演化。在2016年，我們的實驗室已發展出一套工具iPARTS2能透過一級跟三級的結構資訊去對RNA結構做比較。然而，iPARTS2並未考慮它們的二級結構。事實上，許多的研究已經指出比對RNA結構時考慮二級結構資訊是一個有用的策略 。因此，在本研究中。我們開發出一套稱為iPARTS3的工具可以利用一級、二級與三級的結構資訊去比對兩個RNA三級結構。iPARTS3的基本步驟如下：首先我們利用一個結構字元集(structural alphabet)把輸入的RNA三級結構轉成一級的結構字元序列，這個結構字元集是我們在發展iPARTS2時所產生的，它包含92個元素，每個元素皆攜帶著一個代表核苷酸的骨幹幾何與鹼基資訊。接著，我們再把二級結構資訊結合到這些一級結構字元序列成為兩條弧註解序列(arc-annotated sequences)。最後，我們利用傳統的二級結構比對演算法比較弧註解序列以找出兩個RNA三級結構之間的相似度。最後我們的實驗結果證實了iPARTS3在結構相似度上確實比iPARTS2的版本有較好的表現。

It has been realized that RNA is an important molecule in biology because it plays multiple regulated functions in the cell. Basically, functions of RNAs are largely determined by their three dimensional structures. Therefore, developing tools capable of efficiently and accurately comparing the similarity between two RNA 3D structures can help biologist to deeply realize RNA function and evolution. In 2016, our laboratory has developed a tool called iPARTS2 that aligns two RNA 3D structures based on their primary and tertiary structure information. However, iPARTS2 ignores secondary structure information in the RNAs being compared. In fact, several studies have shown that using secondary structure information to compare two RNA tertiary structures is a useful strategy. Therefore, in this study, we develop a tool called iPARTS3, which considers primary, secondary and tertiary structure information to align two RNA 3D structures. The basic steps of iPARTS3 are as follow. First, we reduce input RNA 3D structures into 1D SA-encoded sequences using the structure alphabet, which was constructed by iPARTS2 and consists of 92 elements with each element carrying both information of backbone geometry and base for a representative nucleotide. Then, we incorporate secondary structural information into these 1D SA-encoded sequences to produce arc-annotated sequences. Finally, we use traditional secondary structure alignment algorithm to compare two arc-annotated sequences can find the similarity between RNA 3D structures. Finally, our experimental results have shown that iPARTS3 indeed has better performance than iPARTS2 in terms of quality of structural alignment.

中文摘要 I
Abstract II
Acknowledgement III
Contents IV
List of figures VI
Chapter 1 Introduction 1
Chapter 2 Notations and Method 5
2.1 Notations 5
2.2 Edit operations and problem description 6
2.3 Method 9
2.4 Pseudo code 13
Chapter 3 Experimental results 15
3.1 Testing datasets and method parameters 16
3.2 Experiments 16
3.2.1 Experiment 1 16
3.2.2 Experiment 2 21
Chapter 4 Conclusion 27
References 28

[1] Kolodny,　R. and Linial,　N. (2004) Approximate protein structural alignment in polynomial time. Proceedings of the National Academy of Sciences of the United States of America, 101, 12201–12206.
[2] Capriotti, E. and Marti-Renom, M. A. (2008) RNA structure alignment by a unit-vector approach. Bioinformatics, 24, i112–i118.
[3] Capriotti, E. and Marti-Renom, M. A. (2009) SARA: a server for function annotation of RNA structures. Nucleic Acids Research, 37, W260–W265.
[4] Hoksza, D. and Svozil, D. (2012) Efficient RNA pairwise structure comparison by SETTER method. Bioinformatics, 28, 1858–1864.
[5] Čech, P., Svozil, D. and Hoksza, D. (2012) SETTER: web server for RNA structure comparison. Nucleic Acids Research, 40, W42–W48.
[6] Chung-Han Yang, Cheng-Ting Shih, Kun-Tze Chen, Po-Han Lee, Ping-Han Tsai, Jian-Cheng Lin, Ching-Yu Yen, Tiao-Tin Lin and Chin Lung Lu. (2016) iPARTS2: an improved tool for pairwise alignment of RNA tertiary structures, version 2. NAR, 2016
[7] Jiang,T., Guohui Lin, Bin Ma, and Kaizhong Zhang. (2002) A general edit distance between RNA structures. J. Comput. Biol., 9, 371–388.
[8] Sven Siebert and Rolf Backofen. (2005) MARNA: multiple alignment and consensus structure prediction of RNAs based on sequence structure comparisons. Bioinformatics, 21, 3352-3359.
[9] Subbiah, S., Laurents, D. V. and Levitt, M. (1993) Structural similarity of DNA-binding domains of bacteriophage repressors and the globin core. Current Biology, 3, 141–148.
[10] Kolodny, R., Koehl, P. and Levitt, M. (2005) Comprehensive evaluation of protein structure alignment methods: scoring by geometric measures. Journal of Molecular Biology, 346, 1173–1188.