De novo antibody design

De novo antibody design aims to create antibodies purely in silico that are capable of binding antigens at predefined epitopes in user-specified ways.

Summary of methods

• Backpropagation-based
  • Germinal (1)
  • BoltzDesign (2)
• Diffusion-based
  • RF-antibody (3)
  • DiffAb
  • IgGM
• Hallucination-based
  • BoltzGen
  • Boltz (but requires structure-based sequence design; (4))
• Unknown due to proprietary methods
  • Chai-2
  • JAM-2 (Nabla)

1.

Mille-Fragoso LS, Driscoll CL, Wang JN, Dai H, Widatalla T, Zhang JL, et al. Efficient generation of epitope-targeted de novo antibodies with Germinal. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.09.19.677421

2.

Cho Y, Pacesa M, Zhang Z, Correia BE, Ovchinnikov S. Boltzdesign1: Inverting All-Atom Structure Prediction Model for Generalized Biomolecular Binder Design. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.04.06.647261

3.

Bennett NR, Watson JL, Ragotte RJ, Borst AJ, See DL, Weidle C, et al. Atomically accurate de novo design of antibodies with RFdiffusion. Nature. 2025;649(8095):183–93. Available from: https://doi.org/10.1038/s41586-025-09721-5

4.

Wohlwend J, Corso G, Passaro S, Getz N, Reveiz M, Leidal K, et al. Boltz-1 Democratizing Biomolecular Interaction Modeling. openRxiv; 2024. Available from: https://doi.org/10.1101/2024.11.19.624167