Designing protein domains with ESM3: function depends on the neighborhood, not isolation

bravo_abad · x · 2026-09-25

In his AI-for-Science newsletter, Jorge Bravo Abad highlights a protein design paper by Bülbül et al. that uses ESM3, ProteinMPNN and EvoDiff to generate new thiolation domains for non-ribosomal peptide synthetases. The key insight: instead of designing a domain in isolation, the authors keep its neighboring structure intact, since a domain's function can depend on what sits next to it — protein domains are not necessarily reusable Lego bricks. He collects such transferable ideas beyond the original papers.

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