Abstract
Abstract
Designed binders are routinely filtered on predicted interface confidence, which reports how self-consistently a model places an interface, not where it lies. We designed 200 nanobody loops against the survivin BIR-domain groove, co-folded 196, and checked epitope contact in every predicted complex. Confidence showed no detectable association with epitope engagement (ρ = +0.100, 95% CI −0.04 to +0.24,
n
= 196); its highest and lowest quartiles failed alike (odds ratio 0.97, 95% CI 0.41 to 2.26). It tracked instead the run’s other confidence estimates (ρ = +0.61). Twelve-seed replication separated two candidates the criteria had not: one reached the complete epitope in 10 of 12 runs, the other never. Across 155 predictions the top-ranked model was no better than one drawn at random from its five (
P
= 0.610), though only 3 of 31 failed on every model. Nothing was assayed; nb_cand_057 is an in silico candidate only.