Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments

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

With the recent focus on nonprotein coding RNA (ncRNA) genes, interest in detecting novel ncRNAs has rapidly emerged. Since the structure of RNA is evolutionarily more conserved than its sequence, predicting the RNA's secondary structure is one of the most important steps towards its functional analysis. There are two fundamentally different approaches to predicting RNA secondary structures, namely free-energy minimization and probabilistic approaches, which often use phylogenetic information given by a multiple sequence alignment. This duality of approaches represents two different types of RNA structure information, the former relies on the physical properties of single sequences, while the latter uses evolutionary information in the form of compensatory base pair substitutions.