RNA molecules are hugely important in the biology of the cell. Besides their rather simple role as an intermediate messenger between DNA and protein, RNA molecules can have a plethora of biologic functions. Well known examples of this are the infrastructural RNAs such as tRNAs, rRNAs and snRNAs, but the existence and functionality of several other groups of non-coding RNAs are currently being discovered. These include micro- (miRNA), small interfering- (siRNA), Piwi interacting- (piRNA) and small modulatory RNAs (smRNA) [Costa, 2007].
A common feature of many of these non-coding RNAs is that the molecular structure is important for the biological function of the molecule.
Ideally, biological function is best interpreted against a 3D structure of an RNA molecule. However, 3D structure determination of RNA molecules is time-consuming, expensive, and difficult [Shapiro et al., 2007] and there is therefore a great disparity between the number of known RNA sequences and the number of known RNA 3D structures.
However, as it is the case for proteins, RNA tertiary structures can be characterized by secondary structural elements. These are defined by hydrogen bonds within the molecule that form several recognizable "domains" of secondary structure like stems, hairpin loops, bulges and internal loops (see below). Furthermore, the high degree of base-pair conservation observed in the evolution of RNA molecules shows that a large part of the functional information is actually contained in the secondary structure of the RNA molecule.
Fortunately, RNA secondary structure can be computationally predicted from sequence data allowing researchers to map sequence information to functional information. The subject of this paper is to describe a very popular way of doing this, namely free energy minimization. For an in-depth review of algorithmic details, we refer the reader to [Mathews and Turner, 2006].