Structure-based self-supervised learning enables ultrafast protein stability prediction upon mutation.

ABSTRACT: Predicting free energy changes (ΔΔG) is essential for enhancing our understanding of protein evolution and plays a pivotal role in protein engineering and pharmaceutical development. While traditional methods offer valuable insights, they are often constrained by computational speed and reliance on biased training datasets. These constraints become particularly evident when aiming for accurate ΔΔG predictions across a diverse array of protein sequences. Herein, we introduce Pythia, a self-supervised graph neural network specifically designed for zero-shot ΔΔG predictions. Our comparative benchmarks demonstrate that Pythia outperforms other self-supervised pretraining models and force field-based approaches while also exhibiting competitive performance with fully supervised models. Notably,

SUBMITTER: Sun J 

PROVIDER: S-EPMC11763918 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature