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Structural alignment
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==RNA structural alignment== Structural alignment techniques have traditionally been applied exclusively to proteins, as the primary biological [[macromolecule]]s that assume characteristic three-dimensional structures. However, large [[RNA]] molecules also form characteristic tertiary [[RNA structure|structures]], which are mediated primarily by [[hydrogen bond]]s formed between [[base pair]]s 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,<ref name="Torarinsson"/> 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 structures 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<ref name="hoksza"/> 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 [http://siret.cz/setter/ SETTER webserver].<ref name="cech"/> A recent method for pairwise structural alignment of RNA sequences with low sequence identity has been published and implemented in the program [http://foldalign.kvl.dk/ FOLDALIGN].<ref name="havgaard"/> 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 [[pseudoknot]]s can often be sensibly predicted using [[Thermodynamic free energy|free energy]]-based scoring methods that account for base pairing and stacking.<ref name="Mathews"/>
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