Abstract
RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here a third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures of riboswitch aptamers and puzzle 7, a ribozyme structure, are included in this round of the experiment. The riboswitch structures include biological binding sites for small molecules (S-adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5′-triphosphate, glutamine) and proteins (YbxF), and one set describes large conformational changes between ligand-free and ligand-bound states. The Varkud satellite ribozyme is the most recently solved structure of a known large ribozyme. All puzzles have established biological functions and require structural understanding to appreciate their molecular mechanisms. Through the use of fast-track experimental data, including multidimensional chemical mapping, and accurate prediction of RNA secondary structure, a large portion of the contacts in 3D have been predicted correctly leading to similar topologies for the top ranking predictions. Template-based and homology-derived predictions could predict structures to particularly high accuracies. However, achieving biological insights from de novo prediction of RNA 3D structures still depends on the size and complexity of the RNA. Blind computational predictions of RNA structures already appear to provide useful structural information in many cases. Similar to the previous RNA-Puzzles Round II experiment, the prediction of non-Watson–Crick interactions and the observed high atomic clash scores reveal a notable need for an algorithm of improvement. All prediction models and assessment results are available at http://ahsoka.u-strasbg.fr/rnapuzzles/.
Highlights
Our growing knowledge of the biological functions of RNA demands an increased rate of modeling the structures of RNA
One of the aims of computational predictions of 3D RNA structure is to help in the understanding of the binding of small RNA molecules, the conformational changes induced and in fine to contribute to the unraveling of the molecular mechanisms of riboswitches
Different metrics were used to assess different aspects of the predictions: root mean square deviation (RMSD) stands for the global similarity of all the atoms; deformation index (DI) and the complete deformation profile matrix (DP) stand for prediction accuracy of the nucleotide interactions, while the interaction network fidelity (INF) assesses the interaction accuracies at different levels (Parisien et al 2009); the Clash score evaluated by MolProbity (Chen et al 2010) assesses the atomic harmony of the structure, and the mean of circular quantities (MCQ) score (Zok et al 2014) assesses the structural similarity with the native structure in the torsion angle space
Summary
Our growing knowledge of the biological functions of RNA demands an increased rate of modeling the structures of RNA. A riboswitch undergoes conformational changes upon ligand binding and functions as a switch in transcriptional or translational levels. Aptamers are regions of RNA that selectively bind small molecules, whereas riboswitches are natural RNA aptamers. Available online through the RNA Open Access option. Since riboswitches are functional and may include conformational changes, the 3D structures of riboswitches are of vital importance for understanding the molecular mechanisms of their regulatory functions. One of the aims of computational predictions of 3D RNA structure is to help in the understanding of the binding of small RNA molecules, the conformational changes induced and in fine to contribute to the unraveling of the molecular mechanisms of riboswitches
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