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评估BindCraft用于高亲和性的生成设计

Mike Filius^1,2, Thanasis Patsos^1,2, Hugo Minnee^1,2

¹Leiden Academic Center for Drug Research, Leiden University, Leiden 2333 CC, The Netherlands.

ACS chemical biology

|November 18, 2025

概括

BindCraft是一个生成人工智能平台,通过分析蛋白质结构,成功地设计了用于药物发现的高 afinity . 这种方法对开发针对MDM2和WDR5.5等标的新疗法充满希望.

科学领域:

计算生物学是一种计算生物学.
药物发现药物发现
蛋白质工程是一种蛋白质工程.

背景情况:

从蛋白质结构中开发高亲缘关系联体至关重要,但具有挑战性.
短具有治疗潜力,但由于缺乏稳定的结构,新的功能性的产生是困难的.

研究的目的:

评估BindCraft,一个结构导向的生成建模平台,用于新的体设计和高亲和度联体发现.
评估BindCraft产生的功能性的能力,仅基于目标蛋白质结构.

主要方法:

利用BindCraft,一个结构引导的生成AI平台,用于新的体设计.
合成并经过实验验证的产生的酸对抗瘤学点MDM2和WDR5.5.
采用竞争分析和亲和度测量 (K_D) 来确认结合特异性和强度.

主要成果:

BindCraft为MDM2产生了70种独特的;15种合成中的7种显示了纳米分子亲和力和特定位点的结合.
在9种为WDR5设计的中,有6种与MYC结合部位的亚微分子亲和力结合.
使用BindCraft预测的类优化提高了WDR5绑定器功效的6倍,达到39nM的K_D.

结论:

BindCraft在产生针对特定蛋白质标的高亲和方面取得了显著的成功,与传统显示技术相竞争.
该平台显示了加速开发基于的治疗方法的潜力.
需要进一步评估,因为BindCraft在本研究中没有为PD-1和PD-L1目标产生结合剂.

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