Kappel, K. et al. Proc. Natl Acad. Sci. USA 116, 8336–8341 (2019).

Interactions between RNAs and proteins play a role in most major cellular processes. Because of their importance, scientists have studied them experimentally at close to a genome-wide scale in order to better understand the rules governing these interactions and their associated energetics. They have also been modeled computationally, but this is challenging because RNAs can exist in multiple unbound states and RNA–protein interactions are often associated with large conformational changes. To address this challenge, Kappel et al. developed the Rosetta-Vienna RNP-ΔΔG method to predict RNA–protein binding affinities. This structure-based framework marries secondary-structure-based calculations of unbound RNA free energies and a unified energy function for bound complexes. The researchers showed that the predicted binding energies have low errors for a diverse set of complexes, and further validated the approach by showing accurate predictions for PUM2 binding to hundreds of RNA sequences.