Evaluation of in silico tools for RNA secondary structures determination, using the Hepatitis C Virus IRES sequence as a model

The Ribonucleic acid (RNA) is a key molecule in different cellular processes, including catalysis. These functions depend not only on nucleotide sequences but also of RNA secondary structure (2D) [1]; this is the case of the extensively characterized IRES structure (Internal Ribosome Entry Site) in Hepatitis C Virus (HCV) RNA [2]. Although experimental techniques are available for studying molecular conformation and folding, their high cost limits a more extended use, therefore bioinformatics programs are currently used for RNA 2D prediction. How dissimilar methods are used in most available in silico tools [3–7] we evaluated the accuracy of five programs for RNA secondary structure prediction, using a HCV IRES domain II as a model [8]. Among assessed tools, MATLAB v7.10.0™ did not generate the expected shape for HCV domain II, resulting in the lowest Sensitivity (S) and Predictive Positive (PPV) values, while RNAShape 2.1.6, RNAstructure v 5.4 and Assemble 1.0.4 predicted the same topology, failing in pairings C19/G62 and G24/A56. Finally, Assemble 2.0 predicted the most acceptable topology of domain II, with the highest S and PPV values. Conclusion: None of the five programs could totally predict the topology of the structural model used.