ABodyBuilder2 is an antibody-specific deep learning model for rapid, high-accuracy prediction of Fv structures, including all six CDR loops, from paired heavy (H) and light (L) chain sequences. It achieves a mean CDR-H3 backbone RMSD of 2.81 Å on a benchmark of 34 antibodies and produces full all-atom models without requiring MSAs, templates, or external sequence databases. The API returns PDB-format structures suitable for antibody screening, affinity maturation, and structure-guided engineering workflows.
Predict¶
Predict properties or scores for input sequences
- POST /api/v3/abodybuilder2/predict/¶
Predict endpoint for ABodyBuilder2.
- Request Headers:
Content-Type – application/json
Authorization – Token YOUR_API_KEY
Request
params (object, optional) — Configuration parameters:
plddt (bool, default: False) — Whether to include pLDDT scores in the response
seed (int, optional, default: 42) — Random seed for prediction consistency
items (array of objects, max: 1) — Input sequences:
H (string, min length: 1, max length: 2048, required) — Heavy chain amino acid sequence
L (string, min length: 1, max length: 2048, required) — Light chain amino acid sequence
Example request:
- Status Codes:
200 OK – Successful response
400 Bad Request – Invalid input
500 Internal Server Error – Internal server error
Response
results (array of objects) — One result per input item, in the order requested:
pdb (string) — Predicted antibody structure in standard PDB format.
plddt (array of arrays of floats, optional) — Predicted Local Distance Difference Test (pLDDT) scores per residue:
Outer array length: 2 (chains: heavy chain “H”, light chain “L”)
Inner array length: equal to the number of residues in the corresponding chain
Values range: 0.0–100.0 (higher values indicate higher local structure confidence)
Example response:
Performance¶
Runs on CPU-optimized instances (2 vCPUs, 8 GB RAM) without requiring a GPU, enabling cost-efficient large-scale inference for antibody structures
Predictive accuracy (backbone RMSD, Å) on the 34-antibody benchmark: - CDR-H3: 2.81 (vs 2.90 for AlphaFold-Multimer; ~10% lower error than ABlooper, IgFold, EquiFold) - Framework regions: 0.54–0.57 (within typical X-ray experimental error)
Chemical surface and stereochemistry: - All-atom outputs with accurate side-chain torsions (χ1/χ2) and exposed/buried classification comparable to AlphaFold-Multimer - Zero peptide-bond, cis-bond, D-amino acid, or heavy-atom clash violations in benchmarked models after refinement, unlike EquiFold and some other antibody models
Compared to other BioLM structure predictors: - More accurate and substantially faster than AlphaFold2 / AlphaFold-Multimer for antibodies, especially on CDR-H3 - More accurate for antibodies than generalist models such as ESMFold, while being far more suitable for high-throughput antibody-focused workloads
Applications¶
Accurate prediction of antibody variable region (VH/VL) structures for therapeutic design, providing all-atom Fv models that can be used for downstream docking, epitope mapping, and structure-based affinity maturation workflows in antibody discovery pipelines.
Rapid structural modeling of large antibody panels (up to 8 VH/VL pairs per API call, each chain ≤2048 residues), enabling high-throughput triage of candidates from display libraries or immune repertoire sequencing by linking sequence variants to 3D CDR conformations and paratope geometry.
Nanobody and TCR structure prediction via the broader ImmuneBuilder API, allowing teams to use the same interface for single-domain antibodies and TCRs when appropriate, and to compare structural features across immune modalities in multi-format biologics programs.
Use of model-provided residue-level error estimates to filter or down‑weight uncertain regions (especially CDR-H3), helping focus experimental characterization on designs where predicted loop conformations and VH–VL orientations are likely to be reliable.
Limitations include reduced accuracy for highly unusual or very long CDR-H3 loops and lack of explicit antigen context; predicted structures should be combined with experimental data and additional modeling for final drug design and developability assessment.
Limitations¶
Maximum Sequence Length: Each antibody heavy (
H) and light (L) chain sequence must not exceed2048amino acids.Batch Size: The
itemsarray inImmuneBuilderABodyBuilder2PredictRequestsupports a maximum of8antibody sequence pairs per request.Antibody-specific only: ABodyBuilder2 is trained for paired antibody variable domains (VH/VL). It is not suitable for general protein structure prediction or for other immune receptors such as nanobodies or T-cell receptors; use
nanobodybuilder2ortcrbuilder2instead.CDR-H3 edge cases: Although ABodyBuilder2 achieves state-of-the-art average accuracy for CDR-H3, predictions for unusually long or rare CDR-H3 loops (e.g. beyond ~22 residues) may be less reliable than for typical lengths.
No evolutionary data: The model does not use multiple sequence alignments or evolutionary information, so in settings where evolutionary couplings are critical, AlphaFold-Multimer or similar MSA-based methods may give more accurate results.
Output type: The API returns only an all-atom structure in
pdbformat per item. It does not expose per-residue error estimates, embeddings, attention maps, or other internal model features for downstream analysis.
How We Use It¶
ABodyBuilder2 enables rapid, sequence-to-structure modeling of antibody variable regions (VH/VL) through a standardized API, making accurate Fv and CDR, especially CDR-H3, structures available early in antibody discovery and optimization. These structures integrate with BioLM sequence embeddings, developability predictors, and docking/affinity models to prioritize designs, focus library construction, and inform multi-round in vitro campaigns while scaling to large next-generation sequencing repertoires.
Supports high-throughput structural screening of candidate antibodies to accelerate lead selection and maturation.
Provides consistent 3D inputs for downstream property prediction (e.g., stability, liability, epitope/paratope analyses) and ranking.
References¶
Abanades, B., Wong, W. K., Boyles, F., Georges, G., Bujotzek, A., & Deane, C. M. (2023). ImmuneBuilder: Deep-Learning models for predicting the structures of immune proteins. Communications Biology, 6, 575. https://doi.org/10.1038/s42003-023-04927-7
