@article{pacesa_one-shot_2025,
	title = {One-shot design of functional protein binders with {BindCraft}},
	rights = {2025 The Author(s)},
	issn = {1476-4687},
	url = {https://www.nature.com/articles/s41586-025-09429-6},
	doi = {10.1038/s41586-025-09429-6},
	abstract = {Protein–protein interactions are at the core of all key biological processes. However, the complexity of the structural features that determine protein–protein interactions makes their design challenging. Here we present {BindCraft}, an open-source and automated pipeline for de novo protein binder design with experimental success rates of 10–100\%. {BindCraft} leverages the weights of {AlphaFold}2 (ref. 1) to generate binders with nanomolar affinity without the need for high-throughput screening or experimental optimization, even in the absence of known binding sites. We successfully designed binders against a diverse set of challenging targets, including cell-surface receptors, common allergens, de novo designed proteins and multi-domain nucleases, such as {CRISPR}–Cas9. We showcase the functional and therapeutic potential of designed binders by reducing {IgE} binding to birch allergen in patient-derived samples, modulating Cas9 gene editing activity and reducing the cytotoxicity of a foodborne bacterial enterotoxin. Last, we use cell-surface-receptor-specific binders to redirect adeno-associated virus capsids for targeted gene delivery. This work represents a significant advancement towards a ‘one design-one binder’ approach in computational design, with immense potential in therapeutics, diagnostics and biotechnology.},
	pages = {1--10},
	journaltitle = {Nature},
	author = {Pacesa, Martin and Nickel, Lennart and Schellhaas, Christian and Schmidt, Joseph and Pyatova, Ekaterina and Kissling, Lucas and Barendse, Patrick and Choudhury, Jagrity and Kapoor, Srajan and Alcaraz-Serna, Ana and Cho, Yehlin and Ghamary, Kourosh H. and Vinué, Laura and Yachnin, Brahm J. and Wollacott, Andrew M. and Buckley, Stephen and Westphal, Adrie H. and Lindhoud, Simon and Georgeon, Sandrine and Goverde, Casper A. and Hatzopoulos, Georgios N. and Gönczy, Pierre and Muller, Yannick D. and Schwank, Gerald and Swarts, Daan C. and Vecchio, Alex J. and Schneider, Bernard L. and Ovchinnikov, Sergey and Correia, Bruno E.},
	urldate = {2025-08-28},
	date = {2025-08-27},
	langid = {english},
	keywords = {Biochemistry, Protein design},
}