Recent issue of Nucleic Acids Research has published a paper titled “FRET-guided selection of RNA 3D structures” by Mirko Weber, Felix Erichson, Maciej Antczak, Vanessa Schumann, Josephine Meitzner, Tomasz Zok, Fabio D. Steffen, Marta Szachniuk, and Richard Börner.

The work focuses on computational prediction of the 3D organization of RNA molecules. This is a notoriously difficult problem because RNAs are inherently dynamic, often existing in a wide range of conformational states rather than a single static structure. To overcome the limitations of traditional single-state modeling, the researchers developed an integrative workflow that combines computational prediction with experimental single-molecule FRET (smFRET) data. The study utilized popular prediction tools, including RNAComposer (developed in our Institute), FARFAR2, and AlphaFold3, to generate vast collections of candidate conformations.

By applying the FRETraj tool to simulate FRET distributions and weighting them against experimental results, the team was able to select structure collections that faithfully reflect the RNA’s behavior in solution. This approach represents a paradigm shift in RNA structural biology, moving away from finding a single “best” model toward identifying collections of structures that capture the real-world flexibility of motifs like the GAAA tetraloop.

Link to the publication: https://doi.org/10.1093/nar/gkag147

Congratulations to the entire international team on this foundational achievement!