RNAstructure

RNAstructure's AccessFold is a software tool for predicting base pairs between RNA molecules, specifically those formed between two interacting sequences. The software package provides two algorithms to evaluate accessibility, which can predict binding sites split by unimolecular structures.

Predicting base pairs formed between two interacting RNA sequences remains challenging due to the competition between unimolecular and bimolecular structures. RNAstructure's AccessFold overcomes this challenge by utilizing two novel approaches to evaluate accessibility: free energy density minimization and pseudo-energy minimization.

Free energy density minimization minimizes the folding free energy change per nucleotide involved in an intermolecular secondary structure. On the other hand, a Pseudo-energy minimization called AccessFold minimizes the sum of free energy change and a pseudo-free energy penalty for the bimolecular pairing of nucleotides that are unlikely to be accessible for bimolecular structure. The pseudo-free energy, derived from unimolecular pairing probabilities, is applied per nucleotide in bimolecular pairs. This approach can predict binding sites that are split by unimolecular structures, which was impossible with previously available methods.

To evaluate the accuracy of RNAstructure's AccessFold, a benchmark set of 17 bimolecular RNA structures was assembled. The results showed that AccessFold provides a statistically significant improvement in sensitivity over the method found in a benchmark to be the most accurate previously available method, with an improvement from 36.8% to 57.8% in mean sensitivity for base pair prediction.