Secondary structure losses are required to enforce CDR loopiness during de novo antibody design by hallucination

Summary

Secondary structure losses are required to enforce CDR loopiness during de novo antibody design by hallucination (1). Note that the alpha-helical term was originally introduced in BindCraft (2).

Details

The alpha-helical loss penalizes beta carbon atoms in $i,i+3$ pairs from falling in the 2.0 to 6.2 Å range via the distogram, while the beta-sheet loss penalizes $i,i+3$ pairs from falling in the 9.75 to 11.5 Å range.

Figures

Ref (1)

See also

• Paratope losses are required to enforce CDR-mediated antigen binding during de novo antibody design by hallucination

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.

Pacesa M, Nickel L, Schellhaas C, Schmidt J, Pyatova E, Kissling L, et al. One-shot design of functional protein binders with BindCraft. Nature. 2025;646(8084):483–92. Available from: https://doi.org/10.1038/s41586-025-09429-6