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Structural biology of RNA and protein-RNA complexes after AlphaFold3

Title data

Hennig, Janosch:
Structural biology of RNA and protein-RNA complexes after AlphaFold3.
In: ChemBioChem. (2025) . - e202401047.
ISSN 1439-7633
DOI: https://doi.org/10.1002/cbic.202401047

Abstract in another language

Recent breakthroughs in AI-mediated protein structure prediction have significantly accelerated research and generated valuable hypotheses within the field of structural biology and beyond. Notably, AlphaFold2 has facilitated the determination of larger protein complexes for which only limited experimental data are available. De novo predictions can now be experimentally validated with relative ease compared to the pre-AlphaFold2 era. In May 2024, AlphaFold3 was launched with high expectations, promising the capability to accurately predict RNA structures and protein-RNA complexes - features that were absent in AlphaFold2. This review evaluates the extent to which AlphaFold3 fulfills this promise through specific examples. At present, AlphaFold3 falls short in reliably predicting RNA and protein-RNA complex structures, particularly for non-canonical interactions where training data remain scarce. As a result, users should exercise caution when using AlphaFold3 predictions as hypotheses generators for RNA and protein-RNA complex structures. In the interim, integrating AI-based predictors with data-driven docking tools is recommended to address these limitations. This approach can help bridge the gap until sufficient training data are available to enable the development of more reliable predictive algorithms.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: AlphaFold; RNA dynamics; RNA structure; protein-RNA complexes; structural biology
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry IV - Biophysical Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry IV - Biophysical Chemistry > Chair Biochemistry IV - Biophysical Chemistry - Univ.-Prof. Dr. Janosch Hennig
Research Institutions > Central research institutes > Nordbayerisches Zentrum für NMR-Spektroskopie - NMR-Zentrum
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 500 Natural sciences
500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 17 Feb 2025 09:54
Last Modified: 17 Feb 2025 09:54
URI: https://eref.uni-bayreuth.de/id/eprint/92386