用BindCraft一次性设计功能性蛋白结合物，这一成果由瑞士洛桑理工学院和瑞士生物信息学研究所Bruno E. Correia团队经过不懈努力而取得。2025年8月27日出版的《自然》发表了这项成果。

在这里，该课题组研究人员提出了BindCraft，一个开放的、自动化的管道，用于从头设计蛋白质结合剂，实验成功率为10-100%。BindCraft利用了AlphaFold2的权重。即使在没有已知结合位点的情况下，也不需要高通量筛选或实验优化，生成具有纳米摩尔亲和力的结合物。该课题组成功设计了针对多种具有挑战性靶标的结合物，包括细胞表面受体、常见过敏原、从头设计的蛋白质和多结构域核酸酶，如CRISPR-Cas9。

课题组研究人员通过减少患者来源样本中桦树过敏原的IgE结合，调节Cas9基因编辑活性和降低食源性细菌肠毒素的细胞毒性，展示了设计的结合物的功能和治疗潜力。最后，该研究组将细胞表面受体特异性结合物重新定向腺相关病毒衣壳，以实现靶向基因递送。这项工作代表了计算设计中“一种设计-一种粘合剂”方法的重大进步，在治疗、诊断和生物技术方面具有巨大的潜力。

据介绍，蛋白质之间的相互作用是所有关键生物过程的核心。然而，决定蛋白质相互作用的结构特征的复杂性使得它们的设计具有挑战性。

附：英文原文

Title: One-shot design of functional protein binders with BindCraft

Author: Pacesa, Martin, Nickel, Lennart, Schellhaas, Christian, Schmidt, Joseph, Pyatova, Ekaterina, Kissling, Lucas, Barendse, Patrick, Choudhury, Jagrity, Kapoor, Srajan, Alcaraz-Serna, Ana, Cho, Yehlin, Ghamary, Kourosh H., Vinu, Laura, Yachnin, Brahm J., Wollacott, Andrew M., Buckley, Stephen, Westphal, Adrie H., Lindhoud, Simon, Georgeon, Sandrine, Goverde, Casper A., Hatzopoulos, Georgios N., Gnczy, Pierre, Muller, Yannick D., Schwank, Gerald, Swarts, Daan C., Vecchio, Alex J., Schneider, Bernard L., Ovchinnikov, Sergey, Correia, Bruno E.

Issue&Volume: 2025-08-27

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 AlphaFold2 (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.

DOI: 10.1038/s41586-025-09429-6

Source: https://www.nature.com/articles/s41586-025-09429-6