RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures

Abstract

This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemical-mapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5-3.2 Å, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems. However, the prediction accuracy for non-Watson-Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg.fr/rnapuzzles/.

Keywords: 3D prediction; X-ray structures; bioinformatics; force fields; models; structure quality.

FIGURE 1.

Problem 5: the lariat-capping ribozyme (A) secondary structure and (B) Deformation Profile values for the three predicted models with lowest RMSD: Das model 2 (green), Das model 1 (blue), and Adamiak model 1 (cyan). (Radial red lines) The minimum, maximum, and mean DP values for each domain. (C) Structure superimposition between native structure (green) and best predicted model (blue, Das model 2) with wall–eye stereo representation.

FIGURE 2.

Illustration of the “ring” topology structure in Problem 5. Native structure with “ring” topology is shown in green; the best prediction model Das model 2 and the third best prediction Adamiak model 1 are shown in the same aspect in blue and red, respectively. Although the best model cannot totally capture the “ring” topology, it is more similar to native topology than others.

FIGURE 3.

Problem 6: the adenosylcobalamin riboswitch (A) secondary structure and (B) Deformation Profile values for the three predicted models with lowest RMSD: Das model 4 (green), Das model 6 (blue) and Das model 2 (cyan). (Radial red lines) The minimum, maximum, and mean DP values for each domain. (C) Structure superimposition between native structure (green) and best predicted model (blue, Das model 4) with wall–eye stereo representation.

FIGURE 4.

Problem10: the T-box–tRNA complex (A) secondary structure and (B) Deformation Profile values for the three predicted models with lowest RMSD: Das model 3 (green), Das model 4 (blue), and Das model 1 (cyan). (Radial red lines) The minimum, maximum, and mean DP values for each domain. (C) Structure superimposition between native structure (green) and best predicted model (blue, Das model 3).

FIGURE 5.

Modules in Problem 10. (A) Detailed structure of T-loop of Das model 4, (B) detailed structure of U30 of Das model 4, (C) detailed structure of K-turn of Das model 4, (D) detailed structure of Loop-E of Das model 4.