Back

Distilling Protein Language Models with Complementary Regularizers

Wijaya, E.

2026-02-25 bioinformatics
10.64898/2026.02.17.706304 bioRxiv
Show abstract

Large autoregressive protein language models generate novel sequences de novo, but their size limits throughput and precludes rapid domain adaptation on scarce proprietary data. We distill a 738M-parameter protein language model into compact students using two protein-specific enhancements, uncertainty-aware position weighting and calibration-aware label smoothing, that individually degrade quality yet combine for substantial improvement. We trace this complementary-regularizer effect to information theory: smoothing denoises teacher distributions while weighting amplifies the cleaned signal at biologically variable positions. Students achieve up to 5x inference speedup, preserve natural amino acid distributions, and require as little as 170 MB of GPU memory, enabling deployment on consumer-grade hardware. When fine-tuned on protein families with as few as 50 sequences, students generate more family-matching sequences than the teacher, achieving higher sample efficiency and Pfam hit rates despite their smaller capacity. These results establish distilled protein language models as superior starting points for domain adaptation on scarce data.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.