Impact of the energy model on the complexity of RNA folding with pseudoknots

Predicting the folding of an RNA sequence, while allowing general pseudoknots (PK), consists in finding a minimal free-energy matching of its n positions. Assuming independently contributing base-pairs, the problem can be solved in Θ(n ³)-time using a variant of the maximal weighted matching. By contrast, the problem was previously proven NP-Hard in the more realistic nearest-neighbor energy model. In this work, we consider an intermediate model, called the stacking-pairs energy model. We extend a result by Lyngsø, showing that RNA folding with PK is NP-Hard within a large class of parametrization for the model. We also show the approximability of the problem, by giving a practical Θ(n ³) algorithm that achieves at least a 5-approximation for any parametrization of the stacking model. This contrasts nicely with the nearest-neighbor version of the problem, which we prove cannot be approximated within any positive ratio, unless P = NP.