PRISM-4D enters a hit-to-lead campaign at three distinct points and adds capability that conventional structure-based pipelines don't: target enablement before the screen, pocket-anchored triage after it, and detection of binding sites that static-structure methods miss entirely. End-to-end validation in the bioRxiv preprint runs on a single consumer-grade GPU — the democratization baseline for groups without HPC access — while the same engine supports multi-node scaling and fully air-gapped cleanroom deployment when campaign size or compliance posture requires it.
Pre-screen · Target enablement
Make undruggable targets tractable for the first compound
High-value targets — KRAS isoforms, mutant p53, tau filament, polyQ aggregators, transcription-factor interfaces — expose no obvious druggable pocket in their static structures. Conventional virtual screens against them either fail or return false positives at the orthosteric surface. PRISM-4D analyzes recurrent nonequilibrium dynamics and surfaces cryptic and allosteric pockets with measured persistence, lining residues, and accessibility profile. The output seeds a fresh fragment, virtual, or DEL screen against pockets conventional analyses rule out.
Post-screen · Triage
Pocket-anchored hit organization, not flat enrichment
Hit-to-lead bottlenecks at validation: hundreds of putative binders, limited assay capacity, no rational basis for prioritization beyond raw enrichment. PRISM-4D contributes pocket-level provenance — which hits share a cryptic pocket, which engage an allosteric site, which appear to bind a transient artifact surface. Hits reorganize into pocket-anchored series rather than a flat ranked list, shifting medicinal-chemistry triage from one-off compound assessment to series-level SAR exploration.
Detection
Reach pockets static methods cannot
On a 9-target prediction-locked blind panel: fpocket 22%, P2Rank 38%, PRISM-4D 48%. The additional 10–26 percentage points are cryptic pockets that static-geometry detectors do not recover. Null-control separation is p ≤ 0.001 against a temporal-scramble baseline, with 12.2× PFR enrichment over a permutation null on the same panel. The detection delta matters in programs where one missed pocket is the difference between a viable and a dead campaign.
Deployment · Air-gapped
Nothing leaves the facility
PRISM-4D deploys entirely inside the facility's network boundary — at the consumer-GPU democratization baseline validated in the bioRxiv preprint, at multi-node cluster scale when campaign size demands it, or in a fully isolated cleanroom configuration when compliance posture requires it. Target structures, hit libraries, ADMET tables, and proprietary annotation do not transit external infrastructure — no API calls out, no telemetry, no license-server callback. This is the deployment posture for IP-sensitive programs, sovereign or defense-adjacent research, regulated environments where SaaS uploads trigger compliance review, and any program where data residency is non-negotiable. Deployment surface is identical across the workstation, the multi-GPU rack, and the fully isolated cleanroom terminal: one binary, one driver, one local data store.