The challenge of RNA branching prediction: a parametric analysis of multiloop initiation under thermodynamic optimization

Prediction of RNA base pairings yields insight into molecular structure, and therefore function. The most common methods predict an optimal structure under the standard thermodynamic model. One component of this model is the equation which governs the cost of branching, where three or more helical "arms" radiate out from a multiloop (also known as a junction). The multiloop initiation equation has three parameters; changing those values can significantly alter the predicted structure. We give a complete analysis of the prediction accuracy, stability, and robustness for all possible parameter combinations for a diverse set of tRNA sequences, and also for 5S rRNA. We find that the accuracy can often be substantially improved on a per sequence basis. However, simultaneous improvement within families, and most especially between families, remains a challenge.