Language-based protein folding NNs predict novelty with far lower confidence than MSA-based protein folding NNs

Summary

PLM-based protein folding NNs predict structural novelty with far lower accuracy than MSA-based protein folding NNs (1). This was shown with ESMFold and AlphaFold2 using low-confidence predictions from the ESM Metagenomic atlas, which were re-predicted with AF2.

Figures

Ref (1)

See also

• AlphaFold2 outperforms ESMFold at distinguishing designable and undesignable protein backbones

1.

Yeo J, Han Y, Bordin N, Lau AM, Kandathil SM, Kim H, et al. Metagenomic-scale analysis of the predicted protein structure universe. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.04.23.650224