# Shared latent space affinity prediction

PDZ-binding motifs (PBMs) are short C-terminal sequences that determine which PDZ domains a protein binds. Designing PBMs by affinity has generally required a dedicated model per domain and made off-target control hard. This work encodes PDZ and PBM sequences into one 128-dimensional unit hypersphere, predicts pKd from their cosine similarity, and writes single-target, target-minus-off-target and dual-target-mean objectives as directions on that sphere; in four-position redesign for DLG4-PDZ3, 84 of the top 100 candidates fell in the top 1% of measured fitness in a published mutant library, versus 64 for the comparison method.

PDZ-binding motifs (PBMs) are short C-terminal sequences that determine which PDZ domains a protein binds. Designing PBMs by affinity has generally required a dedicated model per domain and made off-target control hard. This work encodes PDZ and PBM sequences into one 128-dimensional unit hypersphere, predicts pKd from their cosine similarity, and writes single-target, target-minus-off-target and dual-target-mean objectives as directions on that sphere; in four-position redesign for DLG4-PDZ3, 84 of the top 100 candidates fell in the top 1% of measured fitness in a published mutant library, versus 64 for the comparison method.