Accurate Identification of Functional Residues Across the Human Proteome with TAMALE (opens in new tab)

The central challenge of the post-AlphaFold era is the "functional gap". Despite having structure predictions for nearly every human protein, we remain unable to systematically distinguish residues that drive activity from those that merely maintain structural integrity. Here we introduce TAMALE, a machine learning model that calculates graded residue-level functional scores across the human proteome without prior annotation. TAMALE transforms structure models and variant effect predictions t...