Lacuna: Cryptic Binding Pocket Discovery via Conformational Ensemble Analysis

Lacuna discovers cryptic binding pockets in proteins by generating a conformational ensemble, detecting pockets per conformer, clustering across the ensemble, and ranking by a continuous crypticity score. Evaluated on 22 cryptic-pocket apo/holo pairs (7/22, 32% under a size-robust Jaccard-or-centroid criterion; 59% under the legacy size-gameable recall metric). Uses an Anisotropic Network Model backend on CPU (~1-8 s/protein).