This list of RNA structure prediction software is a compilation of software tools and web portals used for RNA structure prediction.

The single sequence methods mentioned above have a difficult job detecting a small sample of reasonable secondary structures from a large space of possible structures. A good way to reduce the size of the space is to use evolutionary approaches. Structures that have been conserved by evolution are far more likely to be the functional form. The methods below use this approach.

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Name	Description	Number of sequences [Note 1]	Alignment [Note 2]	Structure [Note 3]	Knots [Note 4]	Link	References
SQUARNA	Common secondary structure prediction based on a greedy stem formation model	any	No	Yes	Yes	sourcecode	[1]
Carnac	Comparative analysis combined with MFE folding.	any	No	Yes	No	sourcecode, webserver	[49][50]
CentroidAlifold	Common secondary structure prediction based on generalized centroid estimator	any	No	Yes	No	sourcecode	[51]
CentroidAlign	Fast and accurate multiple aligner for RNA sequences	any	Yes	No	No	sourcecode	[52]
CMfinder	an expectation maximization algorithm using covariance models for motif description. Uses heuristics for effective motif search, and a Bayesian framework for structure prediction combining folding energy and sequence covariation.	${\displaystyle 3\leq seqs\leq 60}$	Yes	Yes	No	sourcecode, webserver, website	[53]
CONSAN	implements a pinned Sankoff algorithm for simultaneous pairwise RNA alignment and consensus structure prediction.	2	Yes	Yes	No	sourcecode	[54]
DAFS	Simultaneous aligning and folding of RNA sequences via dual decomposition.	any	Yes	Yes	Yes	sourcecode	[55]
Dynalign	an algorithm that improves the accuracy of structure prediction by combining free energy minimization and comparative sequence analysis to find a low free energy structure common to two sequences without requiring any sequence identity.	2	Yes	Yes	No	sourcecode	[56][57][58]
Foldalign	An algorithm capable of making both local and global pairwise structural alignments of RNAs. Based on a combination of energy minimization of the conserved structure and sequence similarity using ribosum-like scoring matrices. For local alignments more than one alignment can be returned.	2	Yes	Yes	No	sourcecode, webserver, website	[59]
FoldalignM	A multiple RNA structural RNA alignment method, to a large extent based on the PMcomp program.	any	Yes	Yes	No	sourcecode	[60]
FRUUT	A pairwise RNA structural alignment tool based on the comparison of RNA trees. Considers alignments in which the compared trees can be rooted differently (with respect to the standard "external loop" corresponding roots), and/or permuted with respect to branching order.	any	Yes	input	No	sourcecode, webserver	[61][62]
GraphClust	Fast RNA structural clustering method of local RNA secondary structures. Predicted clusters are refined using LocARNA and CMsearch. Due to the linear time complexity for clustering it is possible to analyse large RNA datasets.	any	Yes	Yes	No	sourcecode	[63]
KNetFold	Computes a consensus RNA secondary structure from an RNA sequence alignment based on machine learning.	any	input	Yes	Yes	linuxbinary, webserver	[64]
LARA	Produce a global fold and alignment of ncRNA families using integer linear programming and Lagrangian relaxation.	any	Yes	Yes	No	sourcecode	[65]
LocaRNA	LocaRNA is the successor of PMcomp with an improved time complexity. It is a variant of Sankoff's algorithm for simultaneous folding and alignment, which takes as input pre-computed base pair probability matrices from McCaskill's algorithm as produced by RNAfold -p. Thus the method can also be viewed as way to compare base pair probability matrices.	any	Yes	Yes	No	sourcecode, webserver	[66]
MASTR	A sampling approach using Markov chain Monte Carlo in a simulated annealing framework, where both structure and alignment is optimized by making small local changes. The score combines the log-likelihood of the alignment, a covariation term and the basepair probabilities.	any	Yes	Yes	No	sourcecode	[67][68]
Multilign	This method uses multiple Dynalign calculations to find a low free energy structure common to any number of sequences. It does not require any sequence identity.	any	Yes	Yes	No	sourcecode	[69]
Murlet	a multiple alignment tool for RNA sequences using iterative alignment based on Sankoff's algorithm with sharply reduced computational time and memory.	any	Yes	Yes	No	webserver	[70]
MXSCARNA	a multiple alignment tool for RNA sequences using progressive alignment based on pairwise structural alignment algorithm of SCARNA.	any	Yes	Yes	No	webserver sourcecode	[71]
pAliKiss	pAliKiss predicts RNA secondary structures for fixed RNA multiple sequence alignments, with special attention for pseudoknotted structures. This program is an offspring of the hybridization of RNAalishapes and pKiss.	any	input	Yes	Yes	webserver sourcecode	[18]
PARTS	A method for joint prediction of alignment and common secondary structures of two RNA sequences using a probabilistic model based on pseudo free energies obtained from precomputed base pairing and alignment probabilities.	2	Yes	Yes	No	sourcecode	[72]
Pfold	Folds alignments using a SCFG trained on rRNA alignments.	${\displaystyle \leq 40}$	input	Yes	No	webserver	[73][74]
PETfold	Formally integrates both the energy-based and evolution-based approaches in one model to predict the folding of multiple aligned RNA sequences by a maximum expected accuracy scoring. The structural probabilities are calculated by RNAfold and Pfold.	any	input	Yes	No	sourcecode	[75]
PhyloQFold	Method that takes advantage of the evolutionary history of a group of aligned RNA sequences for sampling consensus secondary structures, including pseudoknots, according to their approximate posterior probability.	any	input	Yes	Yes	sourcecode	[76]
PMcomp/PMmulti	PMcomp is a variant of Sankoff's algorithm for simultaneous folding and alignment, which takes as input pre-computed base pair probability matrices from McCaskill's algorithm as produced by RNAfold -p. Thus the method can also be viewed as way to compare base pair probability matrices. PMmulti is a wrapper program that does progressive multiple alignments by repeatedly calling pmcomp	${\displaystyle 2\leq seqs\leq 6}$	Yes	Yes	No	sourcecode, webserver	[77]
RNAG	A Gibbs sampling method to determine a conserved structure and the structural alignment.	any	Yes	Yes	No	sourcecode	[78]
R-COFFEE	uses RNAlpfold to compute the secondary structure of the provided sequences. A modified version of T-Coffee is then used to compute the multiple sequence alignment having the best agreement with the sequences and the structures. R-Coffee can be combined with any existing sequence alignment method.	any	Yes	Yes	No	sourcecode, webserver	[79][80]
TurboFold	This algorithm predicts conserved structures in any number of sequences. It uses probabilistic alignment and partition functions to map conserved pairs between sequences, and then iterates the partition functions to improve structure prediction accuracy	any	No	Yes	Yes	sourcecode	[81][82]
R-scape	Verify conserved secondary structure by measuring covarying basepairs and their statistical significance compared to pure phylogeny. Will propose a most conserved ("optimized") one if no secondary structure is given.	any	input	Yes	Yes	home page	[83]
RNA123	Included structure based sequence alignment (SBSA) algorithm uses a novel suboptimal version of the Needleman-Wunsch global sequence alignment method that fully accounts for secondary structure in the template and query. It also uses two separate substitution matrices optimized for RNA helices and single stranded regions. The SBSA algorithm provides >90% accurate sequence alignments even for structures as large as bacterial 23S rRNA: ~2,800 nts.	any	Yes	Yes	Yes	webserver
RNAalifold	Folds precomputed alignments using mix of free-energy and covariation measures. Ships with the ViennaRNA Package.	any	input	Yes	No	homepage	[21][84]
RNAalishapes	Tool for secondary structure prediction for precomputed alignments using a mix of free-energy and a covariation measures. Output can be sifted by the abstract shapes concept to focus on major difference in suboptimal results.	any	input	Yes	No	sourcecode, webserver	[85]
RNAcast	enumerates the near-optimal abstract shape space, and predicts as the consensus an abstract shape common to all sequences, and for each sequence, the thermodynamically best structure which has this abstract shape.	any	No	Yes	No	sourcecode, webserver	[86]
RNAforester	Compare and align RNA secondary structures via a "forest alignment" approach.	any	Yes	input	No	sourcecode, webserver	[87][88]
RNAmine	Frequent stem pattern miner from unaligned RNA sequences is a software tool to extract the structural motifs from a set of RNA sequences.	any	No	Yes	No	webserver	[89]
RNASampler	A probabilistic sampling approach that combines intrasequence base pairing probabilities with intersequence base alignment probabilities. This is used to sample possible stems for each sequence and compare these stems between all pairs of sequences to predict a consensus structure for two sequences. The method is extended to predict the common structure conserved among multiple sequences by using a consistency-based score that incorporates information from all the pairwise structural alignments.	any	Yes	Yes	Yes	sourcecode	[90]
SCARNA	Stem Candidate Aligner for RNA (Scarna) is a fast, convenient tool for structural alignment of a pair of RNA sequences. It aligns two RNA sequences and calculates the similarities of them, based on the estimated common secondary structures. It works even for pseudoknotted secondary structures.	2	Yes	Yes	No	webserver	[91]
SimulFold	simultaneously inferring RNA structures including pseudoknots, alignments, and trees using a Bayesian MCMC framework.	any	Yes	Yes	Yes	sourcecode	[92]
Stemloc	a program for pairwise RNA structural alignment based on probabilistic models of RNA structure known as Pair stochastic context-free grammars.	any	Yes	Yes	No	sourcecode	[93]
StrAl	an alignment tool designed to provide multiple alignments of non-coding RNAs following a fast progressive strategy. It combines the thermodynamic base pairing information derived from RNAfold calculations in the form of base pairing probability vectors with the information of the primary sequence.	${\displaystyle \leq 50}$	Yes	No	No	sourcecode, webserver	[94]
TFold	A tool for predicting non-coding RNA secondary structures including pseudoknots. It takes in input an alignment of RNA sequences and returns the predicted secondary structure(s). It combines criteria of stability, conservation and covariation in order to search for stems and pseudoknots. Users can change different parameters values, set (or not) some known stems (if there are) which are taken into account by the system, choose to get several possible structures or only one, search for pseudoknots or not, etc.	any	Yes	Yes	Yes	webserver	[95]
WAR	a webserver that makes it possible to simultaneously use a number of state of the art methods for performing multiple alignment and secondary structure prediction for noncoding RNA sequences.	${\displaystyle 2\leq seqs\leq 50}$	Yes	Yes	No	webserver	[96]
Xrate	a program for analysis of multiple sequence alignments using phylogenetic grammars, that may be viewed as a flexible generalization of the "Pfold" program.	any	Yes	Yes	No	sourcecode	[97]
Alifreefold/AlifreefoldMulti	an alignment-free approach to predict secondary structure from homologous RNA sequences. It computes a representative structure from a set of homologous RNA sequences using sub-optimal secondary structures generated for each sequence. It is based on a vector representation of sub-optimal structures capturing structure conservation signals by weighting structural motifs according to their conservation across the sub-optimal structures.	>5	No	Yes	No	sourcecodesourcecode webserver	[98][99]
Notes [N 1] Number of sequences: <any|num>. [N 2] Alignment: predicts an alignment, <input|yes|no>. [N 3] Structure: predicts structure, <input|yes|no>. [N 4] Knots: Pseudoknot prediction, <yes|no>.

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Many ncRNAs function by binding to other RNAs. For example, miRNAs regulate protein coding gene expression by binding to 3' UTRs, small nucleolar RNAs guide post-transcriptional modifications by binding to rRNA, U4 spliceosomal RNA and U6 spliceosomal RNA bind to each other forming part of the spliceosome and many small bacterial RNAs regulate gene expression by antisense interactions E.g. GcvB, OxyS and RyhB.

The below table includes interactions that are not limited to UTRs.

MicroRNAs regulate protein coding gene expression by binding to 3' UTRs, there are tools specifically designed for predicting these interactions. For an evaluation of target prediction methods on high-throughput experimental data see (Baek et al., Nature 2008),^[125] (Alexiou et al., Bioinformatics 2009),^[126] or (Ritchie et al., Nature Methods 2009)^[127]

Notes

• RNA
• Non-coding RNA
• RNA structure
• Comparison of nucleic acid simulation software
• Comparison of software for molecular mechanics modeling