RNA structure prediction is hard. How much does that matter?
6 hours ago
- #RNA_structure
- #AlphaFold3
- #therapeutics
- RNA structure prediction is challenging due to the limited number and quality of experimentally determined RNA structures in public repositories.
- RNA is highly flexible, with many conformational degrees of freedom, making it difficult to study using traditional methods like X-ray crystallography, cryo-EM, and NMR.
- AlphaFold3 has made progress in RNA structure prediction but does not solve the problem outright, often being outperformed by tailored methods.
- Secondary structure prediction for RNA is relatively accurate and often sufficient for therapeutic applications, while tertiary structure prediction remains difficult and less critical for many use cases.
- Therapeutic applications of RNA, such as mRNA vaccines, ASOs, and siRNAs, primarily rely on secondary structure, whereas aptamers and ribozymes require tertiary structure.
- Tertiary structure is important for rRNA-targeting antibiotics and some viral RNA targets, but its broader therapeutic utility is limited.
- CircRNAs, which are more stable and less immunogenic than linear mRNAs, rely on tertiary structure for their function, highlighting a potential area where improved structure prediction could be valuable.
- Modified nucleotides in therapeutic mRNAs complicate secondary structure prediction, presenting an ongoing challenge for the field.