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Predict a protein’s shape from its sequence

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6 Oct 2026 · Research

Preprint finds AlphaFold 3 leans on the sequence alignment as a shortcut to the global fold ↗

Probing all 48 Pairformer blocks of AlphaFold 3 with causal interventions, Feldman and Skolnick report that without the sequence alignment, local structure mostly survives but long-range topology breaks down. An alignment from another protein with the same fold, given only at aligned columns, lifts median TM-score from 0.44 to 0.72. They say this explains both its accuracy and its limits.

arXiv · A Shortcut to Structure in AlphaFold 3