Training Compute-Optimal Protein Language Models
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Abstract (arXiv)
We explore optimally training protein language models, an area of significant interest in biological research where guidance on best practices is limited. Most models are trained with extensive compute resources until performance gains plateau, focusing primarily on increasing model sizes rather than optimizing the efficient compute frontier that balances performance and compute budgets. Our investigation is grounded in a massive dataset consisting of 939 million protein sequences. We trained over 300 models ranging from 3.5 million to 10.7 billion parameters on 5 to 200 billion unique tokens, to investigate the relations between model sizes, training token numbers, and objectives. First, we observed the effect of diminishing returns for the Causal Language Model (CLM) and that of overfitting for the Masked Language Model~(MLM) when repeating the commonly used Uniref database. To address this, we included metagenomic protein sequences in the training set to increase the diversity and avoid the plateau or overfitting effects. Second, we obtained the scaling laws of CLM and MLM on Transformer, tailored to the specific characteristics of protein sequence data. Third, we observe a transfer scaling phenomenon from CLM to MLM, further demonstrating the effectiveness of transfer through scaling behaviors based on estimated Effectively Transferred Tokens. Finally, to validate our scaling laws, we compare the large-scale versions of ESM-2 and PROGEN2 on downstream tasks, encompassing evaluations of protein generation as well as structure- and function-related tasks, all within less or equivalent pre-training compute budgets.
Key facts. Cited by 11 papers in the map (data through 7 Oct 2026). Builds on 55 of its 96 references that are in the map. First posted on arXiv 4 Nov 2024.
Builds on
55 of 96 references.
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50 most cited of 55 All 55 (JSON)
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Citing papers per year: 2025: 6; 2026: 5.
11 papers.
- 2025Scaling Laws for Optimal Data Mixturescited by 49
- 2025Scaling Laws for Native Multimodal Modelscited by 47
- 2025Computational Protein Science in the Era of Large Language Models (LLMs)cited by 6
- 2025JanusDNA: A Powerful Bi-directional Hybrid DNA Foundation Modelcited by 4
- 2025Are neural scaling laws leading quantum chemistry astray?cited by 1
- 2026Structure-Aware Masking for Protein Representation Learningcited by 1
- 2025Multimodal 3D Genome Pre-trainingcited by 0
- 2026Problems with Chinchilla Approach 2: Systematic Biases in IsoFLOP Parabola Fitscited by 0
- 2026Decomposing the Generalization Gap in PROTAC Activity Prediction: Variance Attribution and the Inter-Laboratory Ceilingcited by 0
- 2026Protein Structure Prediction: From Evolutionary Constraints to Generative Modelingcited by 0
- 2026Compute-Optimal Pretrain--Fine-tune in Ridge Gradient Descentcited by 0
- 2026Compute-Optimal Pretrain--Fine-tune in Ridge Gradient Descent14 Sep 2026
- 2026Protein Structure Prediction: From Evolutionary Constraints to Generative Modeling17 Aug 2026
- 2026Structure-Aware Masking for Protein Representation Learning15 May 2026
- 2026Decomposing the Generalization Gap in PROTAC Activity Prediction: Variance Attribution and the Inter-Laboratory Ceiling12 May 2026
- 2026Problems with Chinchilla Approach 2: Systematic Biases in IsoFLOP Parabola Fits21 Mar 2026
- 2025Are neural scaling laws leading quantum chemistry astray?30 Sep 2025
- 2025Scaling Laws for Optimal Data Mixtures12 Jul 2025
- 2025JanusDNA: A Powerful Bi-directional Hybrid DNA Foundation Model22 May 2025
- 2025Multimodal 3D Genome Pre-training12 Apr 2025
- 2025Scaling Laws for Native Multimodal Models10 Apr 2025
- 2025Computational Protein Science in the Era of Large Language Models (LLMs)17 Jan 2025