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Created on: 06-Aug-2012   Last updated on: 10-Nov-2012 |  How to cite this?
Total resources - 20
A compilation of RNA structure prediction resources
Ramya G (Correspondence: Acharya KK, kshitish@ibab.ac.in)


Important features / utilities*CitationsYear of publicationRank by usage frequency Add comments
1 Mfold
Mfold is a pioneer tool for RNA structure predictions. It uses minimum free energy (MFE) dynamic programming algorithm to calculate secondary structures of RNA.
Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003 Jul 1;31(13):3406-15. PubMed PMID: 12824337; PubMed Central PMCID: PMC169194 Waugh A, Gendron P, Altman R, Brown JW, Case D, Gautheret D, Harvey SC,Leontis N, Westbrook J, Westhof E, Zuker M, Major F. RNAML: a standard syntax for exchanging RNA information. RNA. 2002 Jun;8(6):707-17. PubMed PMID: 12088144; PubMed Central PMCID: PMC1370290. Zuker M, Jacobson AB. Using reliability information to annotate RNA secondary structures. RNA. 1998 Jun;4(6):669-79. PubMed PMID: 9622126; PubMed Central PMCID: PMC1369649.
Mfold is one of the oldest web servers in computational molecular biology.
2 Vienna RNA Package
Apart from free energy minimization, this package uses partition function calculations, stochastic sampling and maximum expected accuracy structure prediction.
Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuste P. Fast folding and comparison of RNA secondary structures. Monatshefte für Chemie. 1994;125:167-188. Hofacker IL. Vienna RNA secondary structure server. Nucleic Acids Res. 2003 Jul 1;31(13):3429-31. PubMed PMID: 12824340; PubMed Central PMCID: PMC169005. Lorenz R, Bernhart SH, Höner Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL. ViennaRNA Package 2.0. Algorithms Mol Biol. 2011 Nov 24;6:26. PubMed PMID: 22115189; PubMed Central PMCID: PMC3319429.
This package is available for download at http://www.tbi.univie.ac.at/~ivo/RNA/. It has the following features. RNAfold (predicts minimum energy secondary structures and pair probabilities); RNAeval (evaluates energy of RNA secondary structures); RNAheat (calculates the specific heat (melting curve) of an RNA sequence); RNAinverse (inverses fold (design) sequences with predefined structure); RNAdistance (compares secondary structures); RNApdist (compares base pair probabilities); RNAsubopt (complete suboptimal foldings); RNAplot (RNA structure drawings in PostScript, SVG, or GML); RNAcofold (predicts hybrid structure of two sequences); RNAduplex (predicts possible hybridization sites between two sequences); RNAup (predicts RNA-RNA interaction sites using accessibilities); RNAalifold (predicts the consensus structure of several aligned sequences); RNAaliduplex (comparative (multiple alignment) version of RNAduplex); RNALfold (predicts locally stable structure of long sequences); RNAplf
3 UNAFold
UNAFold/Unified Nucleic Acid Folding and hybridization package combines free energy minimization, partition function calculations and stochastic sampling to derive stable RNA structures.
Markham NR, Zuker M. UNAFold: software for nucleic acid folding and hybridization. Methods Mol Biol. 2008;453:3-31. PubMed PMID: 18712296. Zuker M, Mathews DH & Turner DH. Algorithms and thermodynamics for RNA secondary structure prediction: A practical guide in RNA biochemistry and biotechnology. NATO ASI Series. 1999; 11-43. Zuker M. Prediction of RNA secondary structure by energy minimization. Methods Mol Biol. 1994;25:267-94. PubMed PMID: 7516239. Jaeger JA, Turner DH, Zuker M. Predicting optimal and suboptimal secondary structure for RNA. Methods Enzymol. 1990;183:281-306. PubMed PMID: 1690335. Zuker M. On finding all suboptimal foldings of an RNA molecule. Science. 1989 Apr 7;244(4900):48-52. Review. PubMed PMID: 2468181.
This is the updated version of popular Mfold, extended to hybridizing two nucleic acids. Other applications include Homodimer Simulations; Hybridization of two different strands; Quikfold (folds two or more short sequences); Two State melting (hybridization); Two-state Folding; Zipfold.
4 RNAstructure
RNAStructure uses a wide range of algorithms including free energy minimization, partition function calculations, stochastic sampling, maximum expected accuracy structure prediction and others.
Reuter JS, Mathews DH. RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics. 2010 Mar 15;11:129. PubMed PMID: 20230624; PubMed Central PMCID: PMC2984261. Mathews DH. RNA secondary structure analysis using RNAstructure. Curr Protoc Bioinformatics. 2006 Mar;Chapter 12:Unit 12.6. PubMed PMID: 18428759.
It has many features, including predicting common structure to two or more sequences, bimolecular secondary structure, Dynalign (Calculates the lowest free energy secondary structures common to two unaligned sequences), Multilign (Predicts low free energy secondary structures common to three or more sequences using progressive iterations of Dynalign), TurboFold (Calculates the conserved structures of three or more unaligned sequences using iteratively refined partition functions) and many more.
5 MC-Fold/MC-Cons
It is based on nucleotide cyclic motifs' algorithms that considers all base-pairing interactions apart from A.U, G.C & G.U.
Parisien M, Major F. The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature. 2008 Mar 6;452(7183):51-5. PubMed PMID: 18322526.
MC-Fold predicts secondary structures from sequence while MC-Sym builds tertiary structures from MC-Fold's secondary structures. Other applications are RNA DOUBLE-HELIX GENERATOR ( generates an MC-Sym script that will build an RNA double-helix); RNA INTERACTION NETWORK FIDELITY (calculates the interaction network fidelity (INF) between two RNA 3-D structures based on their annotations); RNA SEQUENCE MUTATION (mutates the nucleobase identity to the specified sequence into the furnished 3D structure. This is useful to perform point mutations in a structure, or to replace non-canonical nucleobases by standard one.
6 Pknots
It uses a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots.
Rivas E, Eddy SR. A dynamic programming algorithm for RNA structure prediction including pseudoknots. J Mol Biol. 1999 Feb 5;285(5):2053-68. PubMed PMID: 9925784.
It is a downloadable program and a web interface is not available. A number of other programs are available for download. CONSAN (for Pairwise structural RNA alignment); RNABOB (for Fast Pattern searching for RNA secondary structures); NCRNASCAN (for structural RNA genefinder); COVE (for Covariance models of RNA secondary structure) are available.
7 Sfold
It is based on statistical sampling paradigm.
Ding Y, Chan CY, Lawrence CE. Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W135-41. PubMed PMID: 15215366; PubMed Central PMCID: PMC441587.
Applications for rational design of siRNA, antisense oligonucleotides, ribozymes, microRNA and nucleic acid probes by RNA duplex thermodynamics are available.
8 Pfold
Pfold uses stochastic context free grammars and evolutionary models.
Knudsen B, Hein JJ. Using stochastic context free grammars and molecular evolution to predict RNA secondary structure. Bioinformatics. 1999; 15 (6), 446-454. Knudsen B, Hein J. Pfold: RNA secondary structure prediction using stochastic context-free grammars. Nucleic Acids Res. 2003 Jul 1;31(13):3423-8. PubMed PMID: 12824339; PubMed Central PMCID: PMC169020.
It takes an alignment of RNA sequences as input and predicts a common structure for all sequences.
9 CONTRAfold
It is based on probabilistic models built upon stochastic context-free grammars called conditional log-linear models (CLLMs).
Do CB, Foo CS, Batzoglou S. A max-margin model for efficient simultaneous alignment and folding of RNA sequences. Bioinformatics. 2008 Jul 1;24(13):i68-76. PubMed PMID: 18586747; PubMed Central PMCID: PMC2718655. Do CB, Woods DA, Batzoglou S. CONTRAfold: RNA secondary structure prediction without physics-based models. Bioinformatics. 2006 Jul 15;22(14):e90-8. PubMed PMID: 16873527.
RAF, is a downloadable program from the developers of CONTRAfold, for multiple RNA alignment and folding. Given a set of homologous, unaligned RNA sequences, RAF compute a multiple alignment and consensus structure prediction using a progressive simultaneous alignment and folding algorithm.
10 EvoFold
EvoFold uses comparative genomics based on phylogenetic stochastic context-free grammars for identifying conserved functional RNAs.
Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, Kent J, Miller W, Haussler D. Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput Biol. 2006 Apr;2(4):e33. Epub 2006 Apr 21. PubMed PMID: 16628248; PubMed Central PMCID: PMC1440920.
An 8-way human-referenced genomic vertebrate-alignment (which includes human, chimpanzee, mouse, rat, dog, chicken, pufferfish, and zebrafish), is used to predict 48,479 conserved structural regions and is applied to this software.
11 CentroidFold
It uses averaged gamma-centroid estimator, which is a combination of sFold (centroid) and CONTRAfold (MEA).
Hamada M, Kiryu H, Sato K, Mituyama T, Asai K. Prediction of RNA secondary structure using generalized centroid estimators. Bioinformatics. 2009 Feb 15;25(4):465-73. Epub 2008 Dec 18. PubMed PMID: 19095700. Sato K, Hamada M, Asai K, Mituyama T. CENTROIDFOLD: a web server for RNA secondary structure prediction. Nucleic Acids Res. 2009 Jul;37(Web Server issue):W277-80. Epub 2009 May 12. PubMed PMID: 19435882; PubMed Central PMCID: PMC2703931.
It is predominantly used for predicting structures of non coding RNA.
12 RNAshapes
RNAshapes integrates shape abstraction with MFE dynamic programming algorithms.
Steffen P, Voss B, Rehmsmeier M, Reeder J, Giegerich R. RNAshapes: an integrated RNA analysis package based on abstract shapes. Bioinformatics. 2006 Feb 15;22(4):500-3. Epub 2005 Dec 15. PubMed PMID: 16357029.
Other tools available from RNAshapes are pknotsRG (for folding RNA secondary structures, including the class simple recursive pseudoknots); pKiss (for secondary structure prediction including kissing hairpin motifs); paRNAss (to predict conformational switching in RNA); Locomotif (A graphical program for RNA motif search).
13 Foldalign
It is based on a lightweight energy model and sequence similarity. It implements the Sankoff algorithm for simultaneous structural alignment of multiple sequences.
Havgaard JH, Torarinsson E, Gorodkin J. Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix. PLoS Comput Biol. 2007 Oct;3(10):1896-908. Epub 2007 Aug 20. PubMed PMID: 17937495; PubMed Central PMCID: PMC2014794. Torarinsson E, Havgaard JH, Gorodkin J. Multiple structural alignment and clustering of RNA sequences. Bioinformatics. 2007 Apr 15;23(8):926-32. Epub 2007 Feb 25. PubMed PMID: 17324941. Havgaard JH, Lyngsø RB, Gorodkin J. The FOLDALIGN web server for pairwise structural RNA alignment and mutual motif search. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W650-3. PubMed PMID: 15980555; PubMed Central PMCID: PMC1160234.
A new Semi-Automated RNA Sequence Editor called "SARSE" is available from the site.
14 Kinefold
Its results are based on stochastic folding simulations.
Xayaphoummine A, Bucher T, Isambert H. Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W605-10. PubMed PMID: 15980546; PubMed Central PMCID: PMC1160208.
RNA Movies and RnaViz are the RNA secondary structure visualization softwares from the developers of KineFold.
15 Ppfold
Ppfold uses stochastic context free grammars and evolutionary models.
Sükösd Z, Knudsen B, Kjems J, Pedersen CN. PPfold 3.0: fast RNA secondary structure prediction using phylogeny and auxiliary data. Bioinformatics. 2012 Oct 15;28(20):2691-2. doi: 10.1093/bioinformatics/bts488. Epub 2012 Aug 9. PubMed PMID: 22877864. Sükösd Z, Knudsen B, Vaerum M, Kjems J, Andersen ES. Multithreaded comparative RNA secondary structure prediction using stochastic context-free grammars. BMC Bioinformatics. 2011 Apr 18;12:103. PubMed PMID: 21501497; PubMed Central PMCID: PMC3102635.
It is an updated version of Pfold.
16 CentroidHomfold
It is based on posterior decoding techniques, which consider all the suboptimal secondary structures of the target and homologous sequences and all the suboptimal alignments between the target sequence and each of the homologous sequences.
Hamada M, Sato K, Kiryu H, Mituyama T, Asai K. Predictions of RNA secondary structure by combining homologous sequence information. Bioinformatics. 2009 Jun 15;25(12):i330-8. PubMed PMID: 19478007; PubMed Central PMCID: PMC2687982. Frith MC, Hamada M, Horton P. Parameters for accurate genome alignment. BMC Bioinformatics. 2010 Feb 9;11:80. PubMed PMID: 20144198; PubMed Central PMCID: PMC2829014. Hamada M, Yamada K, Sato K, Frith MC, Asai K. CentroidHomfold-LAST: accurate prediction of RNA secondary structure using automatically collected homologous sequences. Nucleic Acids Res. 2011 Jul;39(Web Server issue):W100-6. Epub 2011 May 11. PubMed PMID: 21565800; PubMed Central PMCID: PMC3125741.
CentroidHomfold-LAST is the updated latest version of CentroidHomfold.
17 RSmatch
It aligns RNA secondary structures and finds RNA motifs using position dependent and position independent scoring matrices.
Liu J, Wang JT, Hu J, Tian B. A method for aligning RNA secondary structures and its application to RNA motif detection. BMC Bioinformatics. 2005 Apr 7;6:89. PubMed PMID: 15817128; PubMed Central PMCID: PMC1090556.
The program is downloadable and a web interface is not available.
18 CyloFold
It is based on placement of helices allowing complex pseudoknots.
Bindewald E, Kluth T, Shapiro BA. CyloFold: secondary structure prediction including pseudoknots. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W368-72. Epub 2010 May 25. PubMed PMID: 20501603; PubMed Central PMCID: PMC2896150.
It is built to detect pseudoknots.
19 Crumple
It is built to generate secondary structures for satellite tobacco mosaic virus (STV) particle, in consistent with the available crystallographic structure.
Schroeder SJ, Stone JW, Bleckley S, Gibbons T, Mathews DM. Ensemble of secondary structures for encapsidated satellite tobacco mosaic virus RNA consistent with chemical probing and crystallography constraints. Biophys J. 2011 Jul 6;101(1):167-75. PubMed PMID: 21723827; PubMed Central PMCID: PMC3127170.
It is useful for viral RNA secondary structure predictions; Sliding Windows and Assembly and Helix Find and Combine are other tools available from the site.
20 RNA123
It is based on homology modelling.
Not available
Not available
Software has to be purchased.
copyright © Dr. Kshitish Acharya K; all rights reserved

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