// Single-seq arm · high-confidence prediction · near@1
Near-perfect global structure. Still near@1, not strict.
2GIS is the best-quality structure in the v0.2 benchmark by both metrics that matter for the structure prediction step: pLDDT 0.822 and a backbone RMSD of 1.33 Åvs the deposited co-crystal. The rank-1 cluster nonetheless lands at 38% binding-site overlap: above near@1 (30%) but below strict@1 (50%). The pre-pilot screen correctly excludes MSA mode (min_id 0.780, no diverse tail).
Why this case matters: a near-perfect global fold is necessary but not sufficient for strict recovery. What ultimately decides overlap is which residues a cluster contacts — not just where its centroid sits. We surface both metrics so the customer can see when they decouple.
Numbers from locked v0.2 benchmark · strict@K / near@K definitions
RNA pocket discovery
SAM-I riboswitch · 2GIS
Bound by S-adenosyl-L-methionine (PDB ligand SAM). 94 nt RNA target.
Top-3 candidate pockets
ranked by persistence × binding-residue stabilityCartoon backbone of the predicted reference frame. Top-3 pocket residues highlighted as licorice; centroid spheres mark each cluster's geometric centre across the ensemble. Hover a card to isolate that pocket. Toggle the experimental SAM overlay to see where the co-crystal ligand sits relative to the rank-1 cluster.
Sequence with pocket residues highlighted
Methods summary
v0.2 detects cavities on the predicted 3D structure using RNA-tuned fpocket parameters (consistent with the published fpocketR approach, Veenbaas et al. PNAS 2025), samples a 5-frame ANM conformational ensemble, and ranks pockets by structural persistence weighted by binding-residue stability (score = persistence × n_residues_intersected). The cross-frame geometric ranker is the load-bearing contribution: on a 7-target cleft-binder benchmark, RNA-tuned detection alone recovers 0 of 7 at strict@1; the ensemble + ranker lifts recovery to 3 of 7 strict@1 and 6 of 7 near@1. Druggability assessment itself is left to your medicinal-chemistry workflow; we provide the geometric metadata and conformational stability metrics as inputs to it. Computational predictions only — experimental validation is required before use in drug development.
// rank-1 binding-site overlap, this target
+32 pp · NEITHER → NEAR
Binding-mode caveat
Pipeline detects cleft-shaped binding pockets. Groove-binding modes and shallow surface-deformation binding may be missed. Contact us if your target's binding mode is groove-mediated.
Computational predictions only. Experimental validation required before drug-development use.