Publications
Nature biotechnologyJan 2023 DOI:
10.1038/s41587-022-01618-2

Large language models generate functional protein sequences across diverse families

Madani, Ali; Krause, Ben; Greene, Eric R; Subramanian, Subu; Mohr, Benjamin P; Holton, James M; Olmos, Jose Luis; Xiong, Caiming; Sun, Zachary Z; Socher, Richard; Fraser, James S; Naik, Nikhil
Product Used
Genes
Abstract
Deep-learning language models have shown promise in various biotechnological applications, including protein design and engineering. Here we describe ProGen, a language model that can generate protein sequences with a predictable function across large protein families, akin to generating grammatically and semantically correct natural language sentences on diverse topics. The model was trained on 280 million protein sequences from >19,000 families and is augmented with control tags specifying protein properties. ProGen can be further fine-tuned to curated sequences and tags to improve controllable generation performance of proteins from families with sufficient homologous samples. Artificial proteins fine-tuned to five distinct lysozyme families showed similar catalytic efficiencies as natural lysozymes, with sequence identity to natural proteins as low as 31.4%. ProGen is readily adapted to diverse protein families, as we demonstrate with chorismate mutase and malate dehydrogenase.
Product Used
Genes

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