Simultaneous design of scFv loops predicted to lead to more fit sequences

Summary

Simultaneously designing all of the CDRs is predicted to lead to more fit sequences of scFvs and antibodies (1,2). In the latter case, the baseline of designing all three heavy chain CDRs was to take the CDRH3 loop from those full designs and use the native CDRH1 and 2 loops, which could be a flawed baseline.

See also

• Loops from one V-region chain affect the conformations and dynamics of loops in the other chain

1.

Li L, Gupta E, Spaeth J, Shing L, Jaimes R, Engelhart E, et al. Machine learning optimization of candidate antibody yields highly diverse sub-nanomolar affinity antibody libraries. Nature Communications. 2023;14(1). Available from: https://doi.org/10.1038/s41467-023-39022-2

2.

Shanehsazzadeh A, Alverio J, Kasun G, Levine S, Calman I, Khan JA, et al. IgDesign: In vitro validated antibody design against multiple therapeutic antigens using inverse folding. openRxiv; 2023. Available from: https://doi.org/10.1101/2023.12.08.570889