Stochastic modeling of RNA pseudoknotted structures: a grammatical approach

Motivation: Modeling RNA pseudoknotted structures remains challenging. Methods have previously been developed to model RNA stem-loops successfully using stochastic context-free grammars (SCFG) adapted from computational linguistics; however, the additional complexity of pseudoknots has made modeling them more difficult. Formally a context-sensitive grammar is required, which would impose a large increase in complexity. Results: We introduce a new grammar modeling approach for RNA pseudoknotted structures based on parallel communicating grammar systems (PCGS). Our new approach can specify pseudoknotted structures, while avoiding context-sensitive rules, using a single CFG synchronized with a number of regular grammars. Technically, the stochastic version of the grammar model can be as simple as an SCFG. As with SCFG, the new approach permits automatic generation of a single-RNA structure prediction algorithm for each specified pseudoknotted structure model. This approach also makes it possible to develop full probabilistic models of pseudoknotted structures to allow the prediction of consensus structures by comparative analysis and structural homology recognition in database searches.