Pro-PRIME: A general Temperature-Guided Language model to engineer enhanced Stability and Activity in Proteins
Designing protein mutants of both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants of improved stability and activity without any prior experimental mutagenesis data of the specified protein. Leveraging temperature-aware language modeling, PRIME demonstrated superior predictive power compared to current state-of-the-art models on the public mutagenesis dataset over 283 protein assays. Furthermore, we validated PRIME's predictions on five proteins, examining the top 30-45 single-site mutations' impact on various protein properties, including thermal stability, antigen-antibody binding affinity, and the ability to polymerize non-natural nucleic acid or resilience to extreme alkaline conditions. Remarkably, over 30% of the AI-recommended mutants exhibited superior performance compared to their pre-mutation counterparts across all proteins and desired properties. Moreover, we have developed an efficient, and successful method based on PRIME to rapidly obtain multi-site mutants with enhanced activity and stability. Hence, PRIME demonstrates the general applicability in protein engineering.
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