Hierarchical Assembly of RNA Three-Dimensional Structures Based on Loop Templates

The current RNA structure prediction methods cannot keep up the pace of the rapidly increasing number of sequences and the emerging new functions of RNAs. Template-based RNA three-dimensional structure prediction methods are restricted by the limited number of known RNA structures, and traditional motif-based search for the templates does not always lead to successful results. Here we report a new template search and assembly algorithm, the hierarchical loop template-assembly method (VfoldLA). The method searches for templates for single strand loop/junctions instead of the whole motifs, which often renders no available templates, or short fragments (several nucleotides), which requires a long computational time to assemble and refine. The VfoldLA method has the advantage of accounting for local and nonlocal interloop interactions. Benchmark tests indicate that this new method can provide low-resolution predictions for RNA conformations at different levels of structural complexities. Furthermore, the VfoldLA-predicted conformations may also serve as reliable putative models for further structure prediction and refinements. VfoldLA is accessible at http://ma.physics.missouri. edu/vfoldLA.