Sequence-structure relations of pseudoknot RNA

<p>Abstract</p> <p>Background</p> <p>The analysis of sequence-structure relations of RNA is based on a specific notion and folding of RNA structure. The notion of coarse grained structure employed here is that of canonical RNA pseudoknot contact-structures with at most two mutually crossing bonds (3-noncrossing). These structures are folded by a novel, <it>ab initio </it>prediction algorithm, cross, capable of searching all 3-noncrossing RNA structures. The algorithm outputs the minimum free energy structure.</p> <p>Results</p> <p>After giving some background on RNA pseudoknot structures and providing an outline of the folding algorithm being employed, we present in this paper various, statistical results on the mapping from RNA sequences into 3-noncrossing RNA pseudoknot structures. We study properties, like the fraction of pseudoknot structures, the dominant pseudoknot-shapes, neutral walks, neutral neighbors and local connectivity. We then put our results into context of molecular evolution of RNA.</p> <p>Conclusion</p> <p>Our results imply that, in analogy to RNA secondary structures, 3-noncrossing pseudoknot RNA represents a molecular phenotype that is well suited for molecular and in particular neutral evolution. We can conclude that extended, percolating neutral networks of pseudoknot RNA exist.</p

A Seeded Genetic Algorithm for RNA Secondary Structural Prediction with Pseudoknots

This work explores a new approach in using genetic algorithm to predict RNA secondary structures with pseudoknots. Since only a small portion of most RNA structures is comprised of pseudoknots, the majority of structural elements from an optimal pseudoknot-free structure are likely to be part of the true structure. Thus seeding the genetic algorithm with optimal pseudoknot-free structures will more likely lead it to the true structure than a randomly generated population. The genetic algorithm uses the known energy models with an additional augmentation to allow complex pseudoknots. The nearest-neighbor energy model is used in conjunction with Turner’s thermodynamic parameters for pseudoknot-free structures, and the H-type pseudoknot energy estimation for simple pseudoknots. Testing with known pseudoknot sequences from PseudoBase shows that it out performs some of the current popular algorithms

Prediction and statistics of pseudoknots in RNA structures using exactly clustered stochastic simulations

Ab initio RNA secondary structure predictions have long dismissed helices interior to loops, so-called pseudoknots, despite their structural importance. Here, we report that many pseudoknots can be predicted through long time scales RNA folding simulations, which follow the stochastic closing and opening of individual RNA helices. The numerical efficacy of these stochastic simulations relies on an O(n^2) clustering algorithm which computes time averages over a continously updated set of n reference structures. Applying this exact stochastic clustering approach, we typically obtain a 5- to 100-fold simulation speed-up for RNA sequences up to 400 bases, while the effective acceleration can be as high as 100,000-fold for short multistable molecules (<150 bases). We performed extensive folding statistics on random and natural RNA sequences, and found that pseudoknots are unevenly distributed amongst RNAstructures and account for up to 30% of base pairs in G+C rich RNA sequences (Online RNA folding kinetics server including pseudoknots : http://kinefold.u-strasbg.fr/ ).Comment: 6 pages, 5 figure