Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments

Seemann, Stefan E.; Gorodkin, Jan; Backofen, Rolf

The main disadvantage of the Sankoff-like approaches is their high-computational cost. For this reason, a class of methods was developed that saves computational resources by predicting the optimal structure from given RNA alignments, which are usually produced by multiple sequence alignment methods. This approach has proven useful in genomic screens for ncRNAs (23, 24) , despite their limitations in finding RNA structures in more divergent sequences (25) . It has been shown that the quality of the predictions breaks down in cases where sequence identity is <60% (26) . On the other hand, these methods can also be applied to improve the consensus structure prediction in Sankoff-like approaches. The reason is simply that the Sankoff-like approaches usually apply a progressive strategy by combining pairwise alignments to build the final multiple alignment. Thus, consensus structure prediction can be improved when considering the complete phylogenetic information.