Abstract
Determining the RNA secondary structure from sequence data by computational predictions is a long-standing problem. Its solution has been approached in two distinctive ways. If a multiple sequence alignment of a collection of homologous sequences is available, the comparative method uses phylogeny to determine conserved base pairs that are more likely to form as a result of billions of years of evolution than by chance. In the case of single sequences, recursive algorithms that compute free energy structures by using empirically derived energy parameters have been developed. This latter approach of RNA folding prediction by energy minimization is widely used to predict RNA secondary structure from sequence. For a significant number of RNA molecules, the secondary structure of the RNA molecule is indicative of its function and its computational prediction by minimizing its free energy is important for its functional analysis. A general method for free energy minimization to predict RNA secondary structures is dynamic programming, although other optimization methods have been developed as well along with empirically derived energy parameters. In this chapter, we introduce and illustrate by examples the approach of free energy minimization to predict RNA secondary structures.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Brion P, Westhof E (1997) Hierarchy and dynamics of RNA folding. Annu Rev Biophys Biomol Struct 26:113–137
Tinoco I, Bustamante C (1999) How RNA folds. J Mol Biol 293:271–281
Griffiths-Jones S, Bateman A, Marshall M, Khanna A, Eddy SR (2003) Rfam: an RNA family database. Nucleic Acids Res 31:439–441
Nussinov R, Pieczenik G, Grigg JR, Kleitman DJ (1978) Algorithms for loop matchings. SIAM J Appl Math 35:68–82
Waterman MS, Smith TF (1978) RNA secondary structure: a complete mathematical analysis. Math Biosci 42:257–266
Nussinov R, Jacobson AB (1980) Fast algorithm for predicting the secondary structure of single stranded RNA. Proc Natl Acad Sci U S A 77(11):6309–6313
Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9:133–148
Zuker M, Sankoff D (1984) RNA secondary structures and their prediction. Bull Math Biol 46:591–621
Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415
Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structures. Monatsh Chem 125:167–188
Hofacker IL (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31:3429–3431
Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288:911–940
Shapiro BA, Wu J-C, Bengali D, Potts MJ (2001) The massively parallel genetic algorithm for RNA folding: MIMD implementation and population variation. Bioinformatics 17:137–148
McCaskill JS (1990) The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29:1105–1119
Zuker M (1989) On finding all suboptimal foldings of an RNA molecule. Science 244:48–52
Wuchty S, Fontana W, Hofacker IL, Schuster P (1999) Complete suboptimal folding of RNA and the stability of secondary structures. Biopolymers 49:145–165
Steffen B, Voss B, Rehmsmeier M, Reeder J, Giegerich R (2006) RNAshapes: an integrated RNA analysis package based on abstract shapes. Bioinformatics 22(4):500–503
Will S, Reiche K, Hofacker IL, Stadler PF, Backofen R (2007) Inferring non-coding RNA families and classes by means of genome-scale structure-based clustering. PLoS Comput Biol 3(4):e65
Gorodkin J, Hofacker IL, Torarinsson E, Yao Z, Havgaard JH, Ruzzo WL (2010) De novo prediction of structures RNAs from genomic sequences. Trends Biotechnol 28(1):9–20
Markham NR, Zuker M (2008) Software for nucleic acid folding and hybridization. Methods Mol Biol 453:3–31
Lorenz R, Lorenz R, Bernhart SH, Höner zu Siederdissen C, Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL (2011) ViennaRNA package 2.0. algorithms. Mol Biol 6:26
You S, Stump DD, Branch AD, Rice CM (2004) A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis c virus RNA replication. J Virol 78(3):1352–1366
Krol J, Sobczak K, Wilczynska U, Drath M, Janiska A, Kaczynska D, Krzyzosiak WJ (2004) Structural features of microRNA (miRNA) precursors and their relevance to miRNA biogenesis and small interfering RNA/short hairpin RNA design. J Biol Chem 279:42230–42239
Barash D, Churkin A (2011) Mutational analysis in RNAs: comparing programs for RN deleterious mutation prediction. Brief Bioinform 12(2):104–114
Churkin A, Barash D (2008) An efficient method for the prediction of deleterious multiple-point mutations in the secondary structure of RNAs using suboptimal folding solutions. BMC Bioinformatics 9:222
Waldispühl J, Devadas S, Berger B, Clote P (2008) Efficient algorithms for probing the RNA mutational landscape. PLoS Comput Biol 4:e1000124
Churkin A, Gabdank I, Barash D (2011) The RNAmute web server for the mutational analysis of RNA secondary structures. Nucleic Acids Res 39:W92–W99
Levin A, Lis M, Ponty Y, O’Donnell CW, Devadas S, Berger B, Waldispühl J (2012) A global sampling approach to designing and reengineering RNA secondary structures. Nucleic Acids Res 40(20):10041–10052
Shapiro BA (1988) An algorithm for comparing RNA secondary structures. Comput Appl Biosci 4:387–393
Avihoo A, Churkin A, Barash D (2011) RNAexinv: an extended inverse RNA folding from shape and physical attributes to sequences. BMC Bioinformatics 12(319):24
Weinbrand L, Avihoo A, Barash D (2013) RNAfbinv: an interactive Java application for fragment-based design of RNA sequences. Bioinformatics 29(22):2938–2940
Acknowledgments
The authors would like to thank Idan Gabdank and Assaf Avihoo for their assistance in this study. This work was partially supported by the Kreitman Foundation at Ben-Gurion University.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Churkin, A., Weinbrand, L., Barash, D. (2015). Free Energy Minimization to Predict RNA Secondary Structures and Computational RNA Design. In: Picardi, E. (eds) RNA Bioinformatics. Methods in Molecular Biology, vol 1269. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2291-8_1
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2291-8_1
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2290-1
Online ISBN: 978-1-4939-2291-8
eBook Packages: Springer Protocols