宿主-病原体相互作用的AlphaFold模型阐明了分子模仿的流行和结构模式
Delora Baptista1, Lidia Gomez-Lucas2, Jürgen Jänes3,4
1Gulbenkian Institute for Molecular Medicine, Oeiras, Portugal.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
病原体模仿宿主蛋白质使用分子模仿来感染细胞. 这项研究使用AlphaFold来预测宿主-病原体相互作用的结构,揭示了常见的模仿策略和融合进化.
科学领域:
- 结构生物学 结构生物学
- 生物信息学是一种生物信息学.
- 进化生物学 进化生物学
背景情况:
- 病原体通过蛋白质-蛋白质相互作用 (PPI) 利用宿主细胞机械,经常使用分子模拟.
- 对宿主病原体PPI缺乏结构数据,阻碍了对模仿和融合进化的理解.
- 已知有成千上万种宿主病原体PPI,但它们的结构基础在很大程度上仍未被探索.
研究的目的:
- 为了对AlphaFold2和AlphaFold3进行基准测试,以预测宿主-病原体相互作用结构.
- 调查宿主-病原体相互作用中的分子模拟的流行和机制.
- 探索病原体蛋白相互作用接口中融合进化的证据.
主要方法:
- 在已知的宿主病原体PPI上对AlphaFold2和AlphaFold3的性能进行基准测试.
- 6,782个病原体与人类的PPI的大规模结构预测.
- 模仿模式的分类 (域家族,结构图案,线性图案) 和预测相互作用的实验验证.
主要成果:
- 宿主-病原体相互作用的AlphaFold模型可以在依靠信心排名时准确,尽管整体性能低.
- 803个高可信度结构模型用于病原体-人体PPI.
- 病原体蛋白通常针对现有的人类PPI接口,最常见的是线性模拟模拟 (12个验证中的3个).
结论:
- AlphaFold是建模宿主-病原体相互作用和研究分子模仿的一个有价值的工具.
- 融合进化在宿主-病原体相互作用接口中普遍存在.
- 了解模仿机制可以了解感染和宿主防御策略.
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