通过结构驱动的计算工作流程,对表位特异性抗体进行新的设计
Fandi Wu1, Yu Zhao2, JiaXiang Wu2
1Tencent AI for Life Sciences Lab, Shenzhen, China. wufandi@outlook.com.
Nature communications
|December 9, 2025
概括
tFold系统快速设计针对特定目标的高亲和度单克隆抗体 (mAbs). 这种计算工作流加速了用于治疗开发的抗体发现.
科学领域:
- 计算生物学是一种计算生物学.
- 免疫学 免疫学 免疫学
- 药物发现 药物发现
背景情况:
- 准确的抗体-抗原复合体建模对于生物医学研究和抗体治疗至关重要.
- 目前的抗体发现方法,如动物免疫和图书馆查,耗时.
- 预测和设计抗体结构落后于一般蛋白质建模.
研究的目的:
- 介绍tFold系统,用于抗体结构预测和设计的高通量计算工作流.
- 为了证明对治疗相关抗原的单克隆抗体的新设计.
- 验证用于抗体发现的集成计算实验管道的效率.
主要方法:
- 综合抗体结构预测 (tFold-Ab) 和抗体-抗原复合体建模 (tFold-Ag).
- 结构引导的虚拟查和新的表位特异性抗体设计.
- 使用表面等离子体共振 (SPR) 和菌体显示查进行实验验证.
主要成果:
- 成功设计了针对流感血素,PD-1,PD-L1和SARS-CoV-2 RBD的单克隆抗体.
- 设计的抗体实现了纳米分子结合亲缘关系和精确的表位向向.
- 证明了集成计算-实验管道的效率.
结论:
- tFold系统克服了现有的抗体发现方法的局限性.
- 能够对用户定义的表位体进行快速,高通量抗体发现.
- 加快新型抗体治疗药物的开发.
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