IgDesign

Design antibody CDR loops for antibody-antigen complexes using inverse folding.

Docs

Input

Antibody-Antigen Complex

100 credits

Output

Configure input settings on the left, then click "Submit job"

What is IgDesign?

IgDesign is a deep learning model for designing antibody complementarity-determining region (CDR) sequences. Developed by Absci, it uses inverse folding—predicting amino acid sequences from backbone structures—to generate CDR variants that maintain structural compatibility with a target antigen.

The model was experimentally validated against eight therapeutic antigens, achieving successful binder design across multiple targets. In surface plasmon resonance (SPR) experiments, IgDesign-generated antibodies matched or exceeded the binding affinities of clinically validated reference antibodies for targets including CD40 and ACVR2B.

How does IgDesign work?

Inverse folding reverses the typical protein folding problem: instead of predicting structure from sequence, it predicts which sequences would fold into a given structure. For antibodies, this means generating CDR sequences compatible with a known antibody-antigen complex geometry.

IgDesign conditions on three sources of structural information:

Antibody backbone coordinates: The 3D positions of backbone atoms in the heavy and light chains
Antigen sequence and structure: Spatial context from the bound antigen
Framework sequences: The conserved regions flanking the CDRs

The model was pre-trained on general protein structures, then fine-tuned specifically on antibody-antigen complexes from the Structural Antibody Database (SAbDab). Training used antigen holdouts at 40% sequence identity to prevent data leakage.

Autoregressive CDR generation

IgDesign generates CDR residues one position at a time, conditioning each prediction on previously generated residues. The design order (which CDR to generate first, second, third) affects the final sequences—the model explores multiple decoding orders and combines results.

How to use IgDesign online

ProteinIQ runs IgDesign on cloud GPUs, handling model setup and execution without requiring local installation.

Input

Input	Description
`Antibody-Antigen Complex`	PDB structure file or RCSB PDB ID (e.g., `1N8Z`). Must contain heavy chain, light chain, and antigen.

Settings

Chain configuration

Setting	Description
`Heavy chain ID`	Chain identifier for the antibody heavy chain (default `H`). Match the chain ID in the PDB file.
`Light chain ID`	Chain identifier for the antibody light chain (default `L`).
`Antigen chain ID`	Chain identifier for the antigen (default `A`).

Design settings

Setting	Description
`CDR regions to design`	Which heavy chain CDRs to redesign: HCDR1, HCDR2, HCDR3, or any combination. Default is all three.
`Number of sequences`	Sequence variants to generate (1–100, default 10). More variants explore sequence space more thoroughly.
`Sampling temperature`	Controls sequence diversity. Lower (0.1–0.5) produces conservative, high-confidence designs. Higher (1.0–2.0) generates more diverse sequences. Default 0.5.

Output

Results appear as a spreadsheet with one row per generated sequence variant. Columns include:

Column	Description
`hcdr1`, `hcdr2`, `hcdr3`	Designed CDR sequences (for each region selected)
`ce_loss`	Cross-entropy loss—lower values indicate higher model confidence that the sequence matches the structure

Interpreting results

Cross-entropy loss

The ce_loss column reflects how well the generated sequence fits the target backbone structure according to the model. Lower cross-entropy indicates higher confidence. However, low loss does not guarantee binding—experimental validation is always required.

Typical values vary by target complexity:

CE loss	Interpretation
< 1.0	High confidence design
1.0–2.0	Moderate confidence
> 2.0	Lower confidence, consider adjusting temperature or target structure

Selecting candidates

Rank sequences by cross-entropy loss when prioritizing candidates for experimental testing. Consider testing multiple sequences across the confidence range—sometimes higher-diversity sequences (higher temperature) discover unexpected solutions.

Applications

De novo antibody design: Generate entirely new CDR sequences targeting a known antigen epitope
Lead optimization: Improve existing antibodies by sampling CDR variants while preserving the binding mode
Affinity maturation: Explore sequence space around functional antibodies to find higher-affinity variants

Limitations

Requires a starting structure: IgDesign needs an existing antibody-antigen complex as input. It cannot design antibodies from antigen alone—use structure prediction or docking to generate initial complexes.
Heavy chain CDRs only: The current implementation designs heavy chain CDRs (HCDR1/2/3). Light chain CDR design is not supported.
Backbone is fixed: The model designs sequences for a fixed backbone geometry. If the designed sequence would prefer a different backbone conformation, binding may be affected.
No explicit affinity prediction: Cross-entropy loss correlates with structural compatibility, not binding affinity. High-confidence designs still require experimental validation.

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What is IgDesign?