MIRAGE: Measuring Interpolation and Redundancy in Affinity GEneralization

A benchmark for measuring whether a protein–ligand binding-affinity model generalises beyond protein families that are heavily represented in the PDB, or whether its reported accuracy is carried by that redundancy.

Frontier co-folding affinity models (Boltz-2, Nesso-1, …) report Pearson ≈ 0.6 on standard benchmarks. When the same models are stratified by protein-family size, that accuracy is concentrated on well-represented families and collapses to ≈ 0 on singleton families — exactly the case that matters when starting a program against a novel target.

Configs

redundancy (18,759 rows, default)

PDBbind-derived protein–ligand complexes with experimental affinity, annotated with protein-family size so accuracy can be stratified by redundancy.

column	description
id	PDB code
sequence	protein chain (single-letter)
smiles	ligand SMILES (from the deposited structure)
pK	experimental −log10(Kd/Ki/IC50); higher = stronger
affinity_type	Kd / Ki / IC50
year	PDB deposition year
family_id	MMseqs2 30%-identity cluster representative
family_size	number of complexes in that family (the redundancy axis)
redundancy_bin	1, 2-5, 6-20, 21-80, 81-300, 301+
ligand_nn_tanimoto	ECFP4 nearest-neighbour similarity to any other ligand
in_core	member of the balanced 3,360-target quick-eval subset

temporal (649 rows)

One structurally novel, post-2021-09-30 target (OpenBind EV-A71 2A protease), with measured KD and shipped baselines. Tests within-target ranking on data that no model with a ≤ 2021 cutoff could have seen.

column	description
id	Fragalysis code
sequence	target protein
smiles	ligand SMILES
pKD	experimental −log10(KD); higher = stronger
baseline_molecular_weight, baseline_clogp, ref_boltz2	reference predictions

Usage

import mirage

def my_model(sequence, smiles):
    return score               # higher = stronger binder

print(mirage.run_redundancy(my_model).summary())
print(mirage.run_temporal(my_model).summary())

See https://github.com/DeepBio-Scientific/MIRAGE for the harness, baselines, and CLI.

Provenance & licensing

• Redundancy set is derived from PDBbind (protein sequences from the PDB; SMILES from deposited ligands; affinities from PDBbind's curated literature values). Only derived annotations are redistributed here, under MIT. Users should observe PDBbind's own terms when using the underlying structures.
• Temporal set is derived from the OpenBind A71EV2A release (CC0) and its public benchmark repository.

Family sizes are computed with MMseqs2 at 30% sequence identity / 80% coverage.