Structural Alignment - RNA Structural Alignment

RNA Structural Alignment

Structural alignment techniques have traditionally been applied exclusively to proteins, as the primary biological macromolecules that assume characteristic three-dimensional structures. However, large RNA molecules also form characteristic tertiary structures, which are mediated primarily by hydrogen bonds formed between base pairs as well as base stacking. Functionally similar noncoding RNA molecules can be especially difficult to extract from genomics data because structure is more strongly conserved than sequence in RNA as well as in proteins, and the more limited alphabet of RNA decreases the information content of any given nucleotide at any given position.

However, because of the increasing interest in RNA sturctures and because of the growth of the number of experimentally determined 3D RNA structures, few RNA structure similarity methods have been developed recently. One of those methods is, e.g., SETTER which decomposes each RNA structure into smaller parts called general secondary structure units (GSSUs). GSSUs are subsequently aligned and these partial alignments are merged into the final RNA structure alignment and scored. The method has been implemented into the SETTER webserver.

A recent method for pairwise structural alignment of RNA sequences with low sequence identity has been published and implemented in the program FOLDALIGN. However, this method is not truly analogous to protein structural alignment techniques because it computationally predicts the structures of the RNA input sequences rather than requiring experimentally determined structures as input. Although computational prediction of the protein folding process has not been particularly successful to date, RNA structures without pseudoknots can often be sensibly predicted using free energy-based scoring methods that account for base pairing and stacking.