MSAs make AlphaFold3 predictions robust to extensive mutation and deletion

Summary

MSAs make AlphaFold3 predictions substantially more robust to sequence perturbation. With evolutionary context, predicted folds can remain stable after roughly 40% of residues are mutated and about 10% are deleted; without an MSA, perturbing approximately 10% of residues can destroy the predicted fold (1).

See also

• Removing MSAs collapses AlphaFold3’s latent space
• MSA-based structure predictions outperform PLM-based methods

1.

Feldman J, Skolnick J. AlphaInterp: Mechanistic Interpretability of AlphaFold 3 Reveals How Evolutionary Information Shapes Protein Structure Prediction. openRxiv; 2026. Available from: https://doi.org/10.64898/2026.04.22.720175