通过原子灵活性增强抗体-抗原相互作用预测
Sara Joubbi1,2, Alessio Micheli1, Paolo Milazzo1
1Department of Computer Science, University of Pisa, Pisa, Italy.
PLoS computational biology
|October 13, 2025
概括
预测局部距离差异测试 (pLDDT) 得分可以模拟抗体灵活性,以改善抗原结合预测. 这种方法增强了抗体-抗原相互作用模型,对于开发针对HIV和SARS-CoV-2等病原体的治疗方法至关重要.
科学领域:
- 免疫学和计算生物学
- 蛋白质结构和动态 蛋白质结构和动态
背景情况:
- 抗体是疫苗和治疗药物必不可少的关键免疫成分.
- 模拟抗体-抗原相互作用是复杂的,因为抗体的灵活性和动态结合.
- 深度学习已经推进了蛋白质结构的预测,但与抗体-抗原动态斗争.
研究的目的:
- 研究使用预测的局部距离差异测试 (pLDDT) 分数来建模抗体灵活性.
- 增强抗体-抗原 (Ab-Ag) 相互作用的计算建模.
- 改进抗体的工程,以提高对可变病原体的亲和力和范围.
主要方法:
- 使用基于指纹的方法,将pLDDT得分作为残留灵活性指标.
- 研究了灵活性对抗体特异性任务和Ab-Ag相互作用建模的影响.
- 使用接收器操作特征曲线下的面积 (AUC-ROC) 评估模型性能.
主要成果:
- 通过pLDDT得分将灵活性纳入,提高了Ab-Ag相互作用模型的预测精度4%,达到92%的AUC-ROC.
- 在帕拉托普预测中展示了最先进的性能.
- 在抗体建模中,pLDDT得分被证明是对抗体建模中的形状灵活性有价值的代表.
结论:
- 考虑到形状灵活性对于准确的抗体-抗原相互作用建模至关重要.
- pLDDT评分提供了一种实用的方法来表示和优化抗体灵活性.
- 这种方法对对抗HIV和SARS-CoV-2等高度可变的病原体的抗体进行工程具有重大前景.
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