整体分子模拟与抗体交叉反应性相关,在全蛋白质组研究中
James O Wrabl1, Josh Beale1,2, Gabriel Fortunato1,3,4
1Department of Biology, Johns Hopkins University, Baltimore MD, United States.
Frontiers in immunology
|February 26, 2026
概括
蛋白质结合亲和关系涉及形状变化和相互作用. 由于"整体分子模拟" (EMM),抗体可以与不同的蛋白质进行交叉反应,而不是由序列相似性而不是热力学兼容性驱动.
科学领域:
- 免疫学 免疫学 免疫学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 蛋白质与蛋白质结合的能量涉及构造平衡和界面相互作用.
- 抗体与蛋白质的结合通常假定蛋白质的形状变化最小,重点是界面相互作用.
- 分子仿真,即抗体结合不相似的点,表明构造性贡献的作用.
研究的目的:
- 调查抗体与蛋白质结合和分子仿真中的 conformational 贡献的作用.
- 介绍和评估"整体分子模拟" (EMM) 的概念.
- 评估EMM在病毒抗原和人类蛋白质组之间的交叉反应中的流行率.
主要方法:
- 利用一种新的方法来评估蛋白质构成组合之间的热力学兼容性.
- 在全蛋白质组规模上评估了构造组合的结合亲缘关系贡献.
- 开发了一种基于序列的算法,用于识别交叉反应表位的EMM签名.
主要成果:
- 符合性贡献可以显著影响蛋白质结合亲和力.
- 确定了"整体分子模拟" (EMM) 作为病毒和人类蛋白质之间缺乏序列/结构相似性的交叉反应的潜在机制.
- 一个基于序列的算法在11个医学相关的交叉反应表位中,在9个中发现了高于预期的EMM值.
结论:
- 规格平衡在蛋白质结合亲和力中起着至关重要的作用.
- EMM为理解交叉反应提供了一个新的框架,其中热力学特征,而不是序列/结构,驱动模拟.
- 这些发现表明EMM是免疫交叉反应的重要因素.
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