PRISM-4D: Prospective-Retrospective Validation of Spike-Event-Driven Nonequilibrium Molecular Sensing for Cryptic Binding-Site Discovery
PRISM-4D introduces a physics-driven platform that represents ligand accessibility as recurrent nonequilibrium event manifolds rather than as static surface geometry. Strict SR@1 = 0.483 vs fpocket = 0.224 and P2Rank = 0.382 across a 9-target prediction-locked blind panel. Vectorial pharmacophore feature recovery (PFR) recovered 26.9% of holo pharmacophore features from frozen apo manifolds versus 2.2% under a temporal-scramble null (12.2× enrichment; empirical p ≤ 0.001). The complete platform runs on a single consumer-grade GPU and ships with a controlled-access reproducibility package on Zenodo.
0.483
Strict SR@1
12.2×
PFR enrichment
9
Blind targets
p ≤ 0.001
Null separation