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RBX1 RING Domain Binder Design Report

Computational design of protein binders targeting RBX1 using Proteina-Complexa and Germinal pipelines

Target: RBX1 RING Domain

PDB: 2LGV
UniProt: P62877
Residues: 12–108 (97 aa)
Function: E3 ubiquitin ligase (Cullin-RING)
Hotspot residues highlighted in red: D40, R46, D51, E55, E66, E67, W72, R86, K89

Method Comparison Summary

Proteina-Complexa (Method 1)

Best AF3 ipTM: 0.510
Best AF3 Ranking: 0.620
Design type: General protein binders (60–120 aa)

Germinal (Method 2)

Best Cofold ipTM (Chai-1): 0.759
Best Halluc ipTM (AF-M): 0.767
Design type: VHH nanobodies (~130 aa)
Note: Germinal designs are VHH nanobodies (~130 aa), Complexa designs are general protein binders (60–120 aa). Validation methods differ (AF3 vs Chai-1).

Method 1: Proteina-Complexa Pipeline

1

Proteina-Complexa

Flow matching generative model produces backbone structures conditioned on the RBX1 target. 200 samples generated with AF2 reward scoring.

200 backbones
2

ProteinMPNN

Inverse folding model designs sequences for top backbones. 8 sequences sampled per backbone.

80 sequences
3

AlphaFold 3 Validation

Predict complex structures with AlphaFold 3. Evaluate via ipTM, pLDDT, iPAE, and ranking score.

9 validated

Method 2: Germinal Pipeline

1

AF-M Hallucination

AlphaFold-Multimer hallucination generates VHH nanobody backbones and sequences targeting RBX1 hotspot residues.

Hallucinated nanobodies
2

AbMPNN Redesign

Antibody-specific ProteinMPNN redesigns CDR loops and framework residues for improved stability and binding.

5 variants per seed
3

Chai-1 Cofold Validation

Independent structure prediction with Chai-1 cofold. Evaluate binding via ipTM, pLDDT, iPAE, and hotspot contacts.

20 validated

Binder Candidates — AF3 Validation Results

Click any column header to sort. Binder_4 (highlighted) shows the best AF3 metrics overall.

Rank Binder Name Length Complexa Reward Complexa ipTM Complexa pLDDT MPNN Score AF3 ipTM AF3 pTM AF3 pLDDT AF3 iPAE AF3 Ranking Actions
Good (ipTM>0.5, pLDDT>70, iPAE<5) Moderate Poor

Germinal VHH Nanobody Candidates — Chai-1 Cofold Validation

Click any column header to sort. Top candidate (highlighted) shows the best Chai-1 cofold ipTM. All designs are VHH nanobodies (~130 aa).

Rank Name Length Halluc ipTM Halluc pLDDT Cofold ipTM Cofold pLDDT Cofold iPAE Hotspot Contacts Actions
Cofold ipTM > 0.7 / pLDDT > 80 Cofold ipTM > 0.5 / pLDDT > 70 Below threshold