BMC bioinformatics, 28 February 2014, Vol.15, pp.60
RNA molecules, especially non-coding RNAs, play vital roles in the cell and their biological functions are mostly determined by structural properties. Often, these properties are related to dynamic changes in the structure, as in the case of riboswitches, and thus the analysis of RNA folding kinetics is crucial for their study. Exact approaches to kinetic folding are computationally expensive and, thus, limited to short sequences. In a previous study, we introduced a position-specific abstraction based on helices which we termed helix index shapes (hishapes) and a hishape-based algorithm for near-optimal folding pathway computation, called HiPath. The combination of these approaches provides an abstract view of the folding space that offers information about the global features. In this paper we present HiKinetics, an algorithm that can predict RNA folding kinetics for sequences up to several hundred nucleotides long. This algorithm is based on RNAHeliCes, which decomposes the folding space into abstract classes, namely hishapes, and an improved version of HiPath, namely HiPath2, which estimates plausible folding pathways that connect these classes. Furthermore, we analyse the relationship of hishapes to locally optimal structures, the results of which strengthen the use of the hishape abstraction for studying folding kinetics. Finally, we show the application of HiKinetics to the folding kinetics of two well-studied RNAs. HiKinetics can calculate kinetic folding based on a novel hishape decomposition. HiKinetics, together with HiPath2 and RNAHeliCes, is available for download at http://www.cyanolab.de/software/RNAHeliCes.htm.
Nucleic Acid Conformation ; RNA Folding ; Computational Biology -- Methods ; RNA -- Chemistry ; Sequence Analysis, RNA -- Methods
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