Ludaic, M.; Elofsson, A.

Motivation: In recent years, tremendous advances have been made in predicting protein structures and protein-protein interactions. However, progress in predicting the structure of RNA, either alone or in complex with other macromolecules, has been less prominent, although some recent developments have been reported. It remains unclear whether the improved prediction accuracy is sustained for novel RNA structures. Results: Here, we use an independent benchmark to evaluate the performance of the latest methods. First, we show that state-of-the-art methods can sometimes predict the structure of single-chain RNA strands, with accurate models observed for RNAs with well-defined or regular secondary structures. Next, our evaluation was extended to RNA complexes, where prediction accuracy was notably higher for those involving extensive canonical base pairing. Additionally, a structural similarity analysis revealed that prediction success strongly correlates with resemblance to known structures, indicating that current methods recognise recurring motifs rather than generalising to novel folds. Finally, we also noted that the estimation of accuracies for RNA models is far from accurate. Therefore, it is not possible to reliably identify the correctly predicted models with today\'s methods. Availability and Implementation: Code used for running the methods and analyzing the main results is available from https://github.com/iammarcol/RNA-Benchmark and here https://zenodo.org/records/15304777