Search algorithms are more important than language model choice for model-guided protein engineering and design

Summary

Search algorithms are more important parameters than exact protein language models for model-guided engineering and design (1). This was shown with ESM and AbLang, which were barely different from one another, but the latter showed huge differences in success rates depending on whether Beam search or Gibbs sampling was used.

Figures

Ref (1)

See also

• Inference-time scaling of de novo designed proteins is more effective for harder targets

20 March 2026: https://biomlzk.ghost.io/language-models-matter-less-than-search-algorithms-for-difficult-protein-design-tasks/

1.

McCarter C, Bhattacharya N, Ober SW, Elliott H. How to make the most of your masked language model for protein engineering. 2026; Available from: https://arxiv.org/abs/2603.10302