{\alpha}-HMM: A Graphical Model for RNA Folding

The secondary structure of a ribonucleic acid (RNA) is higher order structure over the primary sequence of the molecule. Nucleotides on the sequence physically come close to each other through hydrogen bonds between bases, forming canonical Watson-Crick pairs (A-U and G-C), and the wobble pair (G-U) as the fundamental components of the structure. The secondary structure is the intermediate, to a great extent the scaffold for higher order interactions between nucleotides to generate RNA tertiary, i.e., 3-dimensional, structure [7, 17]. The latter determines important RNA functions in biological processes, not only as a genetic information carrier but also playing catalytic, scaffolding, structural, and regulatory roles [12, 4]. There has been abundant interest in understanding the detailed process and dynamics of how RNA folds into its structure [3]. Computational prediction of RNA secondary structure directly from its primary sequence is a very desirable step toward the prediction of RNA 3D structure. This is evident by the RNA Puzzles, an annual competition to predict RNA 3D structures, in which most of the used methods by participants are proceeded by a phase for secondary structure prediction [24, 22, 23]. These authors contributed equally to this work.