Folding without glutamine: Proteome-scale removal of a canonical amino acid.

Glutamine is the primary proteome-scale recoding candidate in Escherichia coli, with the lowest keep-score, yet its removal preserves native-like protein structures.

• Why it matters: It remains unclear which amino acids are structurally essential across an entire proteome, despite prior demonstrations that reducing the amino-acid alphabet is feasible.
• What they did: The team computed keep-score using ProteinMPNN structure-based probabilities and multiple sequence alignment conservation, then recoded all glutamine across 4,148 Escherichia coli proteins and modeled with AlphaFold2.
• The result: After recoding, 85.5% of models exceeded a TMscore of 0.8, matching the 85.9% baseline, with orthogonal checks showing no systematic misfolding and a glutamine-free TEM-1 β-lactamase retaining ampicillin resistance.

AI summary of the abstract · may contain errors · not medical advice · read the paper.