Summary
The affinity of antibodies and nanobodies can be improved by stabilization. For antibodies, (1,2) achieved this using Protein language models and inverse folding models, respectively, as evidenced by targeting of framework residues. For nanobodies, (3) specifically target residues in FR3 which they call a “stabilization code”.
Figures
Ref (3) — teal and purple are the non-stabilized and stabilized nanobodies, respectively
See also
- Stability-activity trade-off during enzyme design and evolution is highly local and not global
- Mutations that give rise to new functions are not more destabilizing than mutations in general
- Conformational entropy in antibodies is inversely proportional to antigen affinity
1.
Hie BL, Shanker VR, Xu D, Bruun TUJ, Weidenbacher PA, Tang S, et al. Efficient evolution of human antibodies from general protein language models. Nature Biotechnology. 2023;42(2):275–83. Available from: https://doi.org/10.1038/s41587-023-01763-2
2.
Shanker VR, Bruun TUJ, Hie BL, Kim PS. Unsupervised evolution of protein and antibody complexes with a structure-informed language model. Science. 2024;385(6704):46–53. Available from: https://doi.org/10.1126/science.adk8946
3.
Ketaren NE, Fridy PC, Malashkevich V, Sanyal T, Brillantes M, Thompson MK, et al. Unique Binding and Stabilization Mechanisms Employed By and Engineered Into Nanobodies. openRxiv; 2023. Available from: https://doi.org/10.1101/2023.10.22.563475