RNA structure and kinetics including pseudoknots through complete landscape enumeration

Kinetic barriers as well as non-nested loops (pseudoknots) still pose challenges in the accurate prediction of RNA secondary structure. We will (1) develop a physical model to estimate the entropies of complex pseudoknots; and (2) demonstrate that their NP-complete enumeration need not impede their study. Our novel polymer physics model can address arbitrarily complex pseudoknots using only two free parameters corresponding to concrete physical quantities -- over an order of magnitude fewer than the sparsest state-of-the-art phenomenological methods. By coupling this model to exhaustive enumeration of the set of possible structures, we compute the entire free energy landscape of secondary structures resulting from a primary RNA sequence. Despite our model's parametric sparsity, it performs on par or better than previously published methods in predicting both pseudoknotted and non-pseudoknotted structures on a benchmark dataset of RNA structures of ≤ 80 nucleotides. We discuss the implications of the complete enumeration procedure employed for the study of kinetics.