ODesign
latestDesign all-atom protein binders with controlled target sites, lengths, and interaction parameters.
Design all-atom protein binders with controlled target sites, lengths, and interaction parameters.
ODesign is an all-atom generative model for designing protein binders. Built on AlphaFold3-like architecture, it generates binding partners by specifying target epitopes with fine-grained control over interaction sites and binder properties. The model operates at atomic resolution, designing both backbone geometry and sidechain conformations simultaneously.
What distinguishes ODesign from earlier protein design tools is its unified framework for multimodal biomolecular design. While most tools specialize in proteins alone, ODesign handles proteins, nucleic acids, and small molecules within a single generative process, enabling interaction types like protein-binding RNA or DNA-binding ligands that were previously inaccessible.
The system uses diffusion-based generation with conditional control at molecular, motif, and atomic levels. Researchers can design binders for entire protein surfaces or specify precise hotspot residues for targeted interaction design.
ProteinIQ runs ODesign on cloud GPU infrastructure, eliminating the need for local installation or compute resources.
| Input | Description |
|---|---|
Target protein structure | Upload a PDB file, or fetch from RCSB using PDB ID (e.g., 1HSG). Maximum 50 MB. |
| Setting | Description |
|---|---|
Receptor mode | Flexible allows target protein conformational changes during design; Rigid keeps target structure fixed. Flexible mode better captures induced-fit binding but requires more compute. |
Samples per seed | Number of binder designs to generate per random seed (1–10, default 5). Higher values increase diversity but extend runtime. |
Seeds | Random seeds for reproducibility and diversity. Single value (e.g., 42) or comma-separated for multiple runs (e.g., 42,43,44). Each seed produces independent designs. |
Hotspot residues | Target residues for binder interaction (format: A30,A33,A34 or A50-64 for ranges). Leave blank to design binders for the entire target surface. Multiple chains supported (e.g., A100,B50-60). |
Binder length minimum | Minimum binder length in residues (20–200, default 50). |
Binder length maximum | Maximum binder length in residues (50–300, default 100). ODesign samples lengths within this range during generation. |
ODesign generates native mmCIF structures containing the designed binder bound to the target protein. Each output includes:
Multiple structures are returned when using multiple seeds or samples per seed. Download all structures as a ZIP archive or view individual structures in the 3D viewer.
The native output archive preserves original filenames and directory paths, structures, resolved configuration, overrides, execution logs, error reports, and constructed input records. Individual designs keep their existing design_N.cif download names; their metadata also records the native filename and path. The traceback.pkl files contain the source's constructed molecular inputs. They are retained for reproducibility and are not exception logs.
ODesign uses a diffusion-based generative process that progressively denoises random atomic coordinates into structured protein-protein complexes. The model is trained on AlphaFold3-like structure prediction, learning to generate binding partners conditioned on target structures.
Unlike backbone-only methods such as RFdiffusion that generate C-alpha traces requiring separate sidechain packing, ODesign generates full atomic detail in a single pass. This all-atom approach allows the model to account for sidechain interactions during generation rather than post-processing them.
The task-oriented masking mechanism enables control at three levels:
Flexible receptor mode co-generates target-binder interfaces, allowing backbone adjustments in the target protein to accommodate the designed binder. Rigid mode fixes the target structure, generating binders for the provided conformation.
Therapeutic antibody design: Generate novel antibody scaffolds targeting specific epitopes on disease-relevant proteins. Hotspot specification enables focused design for neutralizing epitopes or allosteric sites.
Enzyme inhibitor design: Design protein-based inhibitors for enzyme active sites by specifying catalytic residues as hotspots. Rigid receptor mode maintains catalytic geometry while flexible mode explores induced-fit inhibition.
Protein-protein interaction modulators: Create binders that stabilize or disrupt native protein complexes. Multiple seed generation produces diverse scaffolds for experimental screening.
Nucleic acid-binding protein design: Design proteins that bind DNA or RNA at specified sequences—capabilities not available in protein-only design tools. Useful for genome editing tools and transcription factor engineering.
ODesign returns unranked native CIF designs. The design index is a file index, not a confidence score or binding ranking. Evaluate designs experimentally. Key validation steps:
Not all designs will bind experimentally. Generate multiple seeds and samples to produce diverse candidates for screening, then assess their structural quality and binding experimentally. If inference reports errors while producing some designs, the available designs and native error reports remain in the result.
Computational cost: All-atom generation is slower than backbone-only methods. Expect 20–30 minutes for typical runs with multiple seeds and samples.
No binding affinity prediction: ODesign generates structures but does not predict binding affinity (KD or ΔG). Use docking tools like AutoDock Vina or molecular dynamics simulations for affinity estimation.
Validation required: Generated designs are predictions requiring experimental validation.
Limited post-translational modifications: The model does not account for glycosylation, phosphorylation, or other modifications that may affect binding.
Training data bias: Performance may degrade for target proteins with unusual folds or non-canonical interactions underrepresented in training data.
All-atom SE(3)-equivariant diffusion for unconditional generation, motif scaffolding, and binder design.
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