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We present TT2NE, a new algorithm to predict RNA secondary structures withpseudoknots. The method is based on a classification of RNA structuresaccording to their topological genus. TT2NE guarantees to find the minimum freeenergy structure irrespectively of pseudoknot topology. This unique proficiencyis obtained at the expense of the maximum length of sequence that can betreated but comparison with state-of-the-art algorithms shows that TT2NE is avery powerful tool within its limits. Analysis of TT2NE's wrong predictionssheds light on the need to study how sterical constraints limit the range ofpseudoknotted structures that can be formed from a given sequence. Animplementation of TT2NE on a public server can be found athttp://ipht.cea.fr/rna/tt2ne.php.

TT2NE: A novel algorithm to predict RNA secondary structures with pseudoknots