Nature Communications

A machine learning method for calculating highly localized protein stabilities

2026-09-01

The residue-level free energy of opening (∆G op ) is the thermodynamic descriptor of localized protein stability, providing valuable information about the protein ensemble at physiologically relevant timescales and conditions. PFNet instantly determines ∆G op for arbitrarily large proteins and complexes from conventional peptide-level hydrogen exchange-mass spectrometry (HX-MS) datasets. It unlocks the full potential of HX-MS, democratizing the method and establishing quantitative, scalable and accessible analysis.

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DOI https://doi.org/10.1038/s41467-026-75590-9