The Forgetting-Learning Trade-off: Making Reinforcement Learning Work for Protein Language Models
Open Access
- 8 August 2026
- conference paper
- Published by Association for Computing Machinery (ACM)
- p. 10520-10531
Abstract
Reinforcement learning (RL) is increasingly applied to Protein Language Models (PLMs), yet its effectiveness varies across tasks, and standard metrics such as pass@k can rise even when the model's solvable problem set is shrinking. We introduce two capability-level diagnostics. The Expansion-Shrinkage Ratio (ESR) measures how RL shifts the set of problems a PLM can solve, separating genuine gain from probability redistribution. Dual-Reward ESR reports ESR under both the training reward and an orthogonal evaluator; the gap ΔESR quantifies reward hacking as a single observable number. Applied across four protein design tasks, three RL algorithms (DPO, PPO, GRPO), and two PLM architectures, the diagnostics reveal that RL on PLMs is governed by two reward properties: verifiability, whether the reward is a fixed environment or a learned surrogate vulnerable to distribution shift, and coverage, the fraction of sequence space giving an informative gradient. The two axes produce three regimes with distinct ΔESR signatures: well-covered verifiable rewards yield genuine expansion; sparse verifiable rewards induce a coverage bottleneck; predicted rewards induce reward hacking. Controlled analyses isolate these two factors as operative, letting practitioners predict an RL run's outcome before committing to costly fine-tuning.Keywords
Funding Information
- Research Grants Council of the Hong Kong Special Administrative Region, China (T45-401\/22-N)
- Young Scientists Fund (C Class) of the National Natural Science Foundation of China (62506154)
- Fundamental Research Funds for the Central Universities and Nanjing University International Collaboration Initiative (020214380129)
- National Natural Science Foundation of China (B26023)
This publication has 16 references indexed in Scilit:
- DeepSeek-R1 incentivizes reasoning in LLMs through reinforcement learningNature, 2025
- Reinforcement Learning-Based Target-Specific De Novo Design of Cyclic Peptide BindersJournal of Medicinal Chemistry, 2025
- Sequence-only prediction of binding affinity changes: a robust and interpretable model for antibody engineeringBioinformatics, 2025
- Self-play reinforcement learning guides protein engineeringNature Machine Intelligence, 2023
- AB-Gen: Antibody Library Design with Generative Pre-Trained Transformer and Deep Reinforcement LearningGenomics, Proteomics & Bioinformatics, 2023
- T-Cell Receptor Optimization with Reinforcement Learning and Mutation Polices for Precision Immunotherapy2023
- ProteinBERT: a universal deep-learning model of protein sequence and functionBioinformatics, 2022
- CATH: increased structural coverage of functional spaceNucleic Acids Research, 2020
- A topology-based network tree for the prediction of protein–protein binding affinity changes following mutationNature Machine Intelligence, 2020
- AB ‐Bind: Antibody binding mutational database for computational affinity predictionsProtein Science, 2015