// MSA path · longest target · pre-pilot screen passed
161 nucleotides, deep MSA — the opt-in path produces near@1 where single-seq fails.
4GXY is the longest target in the v0.2 benchmark and the only one that triggers the screen on both criteria (min_id 0.705 AND 29.5% homologs in the diverse 70–80% identity band). Single-sequence prediction lands a rank-1 cluster at 18% overlap — neither strict nor near. The MSA-driven path lifts it to 35% overlap: NEAR@1.
4GXY pairs with 4LVV (THF, 50% STRICT under MSA) to define the empirical range over which the opt-in MSA path adds value. Both targets fail single-seq, both pass MSA; the headline numbers span the strict/near boundary.
Numbers from locked v0.2 benchmark · screen methodology
RNA pocket discovery
B12 riboswitch · 4GXY
Bound by cobalamin (family ligand; 4GXY co-crystal binds the designed analog B1Z) (PDB ligand B12). 161 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 B12 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
+35 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.