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Minimum free energy prediction of RNA secondary structures is based on the Nearest Neighbor Thermodynamics Model. While such predictions are typically good, the accuracy can vary widely even for short sequences, and the branching thermodynamics are an important factor in this variance. Recently, the simplest model for multiloop energetics—a linear function of the number of branches and unpaired nucleotides—was found to be the best. Subsequently, a parametric analysis demonstrated that per family accuracy can be improved by changing the weightings in this linear function. However, the extent of improvement was not known due to the ad hoc method used to find the new parameters. Here we develop a branch-and-bound algorithm that finds the set of optimal parameters with the highest average accuracy for a given set of sequences. Our analysis shows that the previous ad hoc parameters are nearly optimal for tRNA and 5S rRNA sequences on both training and testing sets. Moreover, cross-family improvement is possible but more difficult because competing parameter regions favor different families. The results also indicate that restricting the unpaired nucleotide penalty to small values is warranted. This reduction makes analyzing longer sequences using the present techniques more feasible. 

R-loops are nucleic acid structures consisting of a DNA:RNA hybrid and a DNA single strand. They form naturally during transcription when the nascent RNA hybridizes to the template DNA, forcing the coding DNA strand to wrap around the RNA:DNA duplex. Although formation of R-loops can have deleterious effects on genome integrity, there is evidence of their role as potential regulators of gene expression and DNA repair. Here we initiate an abstract model based on formal grammars to describe RNA:DNA interactions and the formation of R-loops. Separately we use a sliding window approach that accounts for properties of the DNA nucleotide sequence, such as C-richness and CG-skew, to identify segments favoring R-loops. We evaluate these properties on two DNA plasmids that are known to form R-loops and compare results with a recent energetics model from the Chédin Lab. Our abstract approach for R-loops is an initial step toward a more sophisticated framework which can take into account the effect of DNA topology on R-loop formation.