ProGen2: Exploring the boundaries of protein language models

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial-intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional fine-tuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. Our models and code are open sourced for widespread adoption in protein engineering. A record of this paper’s Transparent Peer Review process is included in the supplemental information.