Intermolecular binding of RNA molecules is important in a broad spectrum of cases, ranging from mRNA accessibility to siRNA or miRNA binding, RNA probe design, or designing RNA openers [50]. An important question that arises repeatedly is to explain differences in RNA-RNA binding between seemingly very similar or even identical binding sites. As demonstrated e.g. in [22,29,51,52], different RNA secondary structure of the target molecule can have dramatic effects on binding affinities even if the sequence of the binding site is identical.