Do protein representations encode variant function? Diagnosing residue-level protein attributions via embedding-space gradients
A common workflow in protein engineering involves building fitness predictors on protein language models (pLMs) to estimate a variant's fitness and interpret which residues drive it. Attribution methods such as integrated gradients address this second goal by assigning residues contributions to the variant's predicted fitness. However, without ground truth for residue importance, it is unclear…
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