Foldalign: RNA Structure and Sequence Alignment


FOLDALIGN is a tool for aligning RNA structures. It folds and aligns (make a foldalignment) based on a lightweight energy model and sequence similarity. The current version 2.5 makes pairwise foldalignments. The foldalignments can be local and global. Local foldalignments can be extended into scans of the two sequences by limiting the local alignment length. When scanning FOLDALIGN program outputs the best local alignment score for each pair of positions in the two sequences. This list can be further processed to produce a list of non-overlapping local alignments between the two sequences.


FOLDALIGN is available as a software package, or as a web-server.

Abstract from Bioinformatics, 21(9): 1815-1824, 2005

Motivation: Searching for non-coding RNA (ncRNA) genes and structural RNA elements (eleRNA) are major challenges in gene finding today as these often are conserved in structure rather than in sequence. Even though the number of available methods is growing, it is still of interest to pairwise detect two genes with low sequence similarity, where the genes are part of a larger genomic region.

Results: Here we present such an approach for pairwise local alignment which is based on FOLDALIGN and the Sankoff algorithm for simultaneous structural alignment of multiple sequences. We include the ability to conduct mutual scans of two sequences of arbitrary length while searching for common local structural motifs of some maximum length. This drastically reduces the complexity of the algorithm. The scoring scheme includes structural parameters corresponding to those available for free energy as well as for substitution matrices similar to RIBOSUM. The new FOLDALIGN implementation is tested on a dataset where the ncRNAs and eleRNAs have sequence similarity <40% and where the ncRNAs and eleRNAs are energetically indistinguishable from the surrounding genomic sequence context. The method is tested in two ways: (1) its ability to find the common structure between the genes only and (2) its ability to locate ncRNAs and eleRNAs in a genomic context. In case (1), it makes sense to compare with methods like Dynalign, and the performances are very similar, but FOLDALIGN is substantially faster. The structure prediction performance for a family is typically around 0.7 using Matthews correlation coefficient. In case (2), the algorithm is successful at locating RNA families with an average sensitivity of 0.8 and a positive predictive value of 0.9 using a BLAST-like hit selection scheme.

Availability: The program is available online at


Foldalign 2.5: multithreaded implementation for pairwise structural RNA alignment

Sundfeld D, Havgaard JH, de Melo AC, Gorodkin J Bioinformatics. 2016 Apr 15;32(8):1238-40. Epub 2015 Dec 24
[ PubMed | Paper | Webserver | Software ]

Comparative ncRNA gene and structure prediction using Foldalign and FoldalignM

Havgaard J, Kaur S, Gorodkin J Curr Protoc Bioinformatics. 2012 Sep;Chapter 12:Unit12.11
[ PubMed | Chapter ]

Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix

Havgaard JH, Torarinsson E, Gorodkin J PLoS Comput Biol. 2007 Oct;3(10):1896-908. Epub 2007 Aug 20
[ PubMed | Paper | Software | Sup ]

Multiple structural alignment and clustering of RNA sequences

Torarinsson E, Havgaard JH, Gorodkin J Bioinformatics. 2007 Apr 15;23(8):926-32. Epub 2007 Feb 25
[ PubMed | Paper ]

The FOLDALIGN web server for pairwise structural RNA alignment and mutual motif search

Havgaard JH, Lyngso RB, Gorodkin J Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W650-3
[ PubMed | Paper | Webserver | Software | Sup ]

Pairwise local structural alignment of RNA sequences with sequence similarity less than 40%

Havgaard JH, Lyngso RB, Stormo GD, Gorodkin J Bioinformatics. 2005 May 1;21(9):1815-24. Epub 2005 Jan 18
[ PubMed | Paper ]