LGJun 17

Be Your Own Teacher: Steering Protein Language Models via Unsupervised Reward Optimization

arXiv:2606.1896112.6
Predicted impact top 26% in LG · last 90 daysOriginality Incremental advance
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This work enables controllable protein generation without costly wet-lab validation or curated preference datasets, addressing a key bottleneck in biomolecular design.

The authors introduce unsupervised reward optimization for protein language models, using intrinsic model uncertainty and extrinsic semantic consistency as proxy rewards. Their methods (SRO and BRO) outperform DPO and KTO on compositional out-of-distribution prompts, approaching oracle performance across multiple temperatures, model scales, and protein families.

Protein language models (PLMs) have emerged as powerful tools for controllable biomolecular design, yet their post-training adaptation typically relies on costly wet-lab validation or curated preference datasets. To overcome this supervision bottleneck, we introduce unsupervised reward optimization of PLMs, a comprehensive framework for steerable protein generation without ground-truth labels. Our key insight is that task-agnostic rewards, which combine intrinsic model uncertainty with extrinsic semantic consistency informed by protein representation models, exhibit strong correlation with controllability measures across base models and temperature regimes. Building upon this discovery, we propose two offline algorithms: Soft Reward Optimization (SRO) and Binarized Reward Optimization (BRO), which effectively maximize the classical RLHF objective induced by these proxy rewards. Extensive experiments on compositional out-of-distribution prompts demonstrate that both methods significantly outperform competitive baselines (DPO, KTO), while approaching oracle performance across multiple sampling temperatures, model scales and protein families. Moreover, PLMs fine-tuned with unsupervised rewards can achieve consistently higher coverage compared to their base model in pass@k evaluations. By enabling self-improvement of PLMs through their own generated experience, our framework provides a scalable pathway toward controllable biomolecular design in settings where labeled preferences or experimental feedback are scarce or unavailable.

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