自由:一个自动化的计算管道指导蛋白质创新的实验测试
Damian Dudka1, R Brian Akins1, Michael A Lampson1
1Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
The Journal of cell biology
|June 26, 2023
概括
我们开发了FREEDA,这是一个可访问的工具来检测蛋白质进化特征. FREEDA揭示了中间体蛋白中的功能性创新,指导了细胞生物学研究.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 细胞生物学家经常忽略了由进化形成的蛋白质创新.
- 检测正选择的计算方法对于非专家来说是复杂的.
- 了解进化创新是解读蛋白质功能的关键.
研究的目的:
- 介绍FREEDA,一个用于检测蛋白质进化中的正选择的自动化管道.
- 为细胞生物学家提供进化分析.
- 识别和实验验证中心蛋白质中的功能性创新.
主要方法:
- 开发了FREEDA,这是一个具有图形界面的用户友好的计算管道.
- 整合了已建立的分子进化工具,以检测各种物种 (动物,灵长类动物,食肉动物,鸟类,) 的积极选择.
- 利用AlphaFold进行蛋白质结构预测,并将进化信号映射到结构上.
主要成果:
- 将FREEDA应用于100多种中间体蛋白质,确定了显著的正选择.
- 检测到古代蛋白质域的循环和轮回中的积极选择,这表明功能性创新.
- 在CENP-O的小鼠中体现了功能性创新,作为原则证明.
结论:
- FREEDA为细胞生物学研究提供了一个可访问的计算工具.
- 该管道有助于发现蛋白质功能的进化创新.
- 实验验证证证实了FREEDA在识别功能相关进化变化的有用性.
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