由原子模拟揭示的内在无序蛋白质的结构和非结构结合
Raúl Esteban Ithuralde1, Adrián Enrique Roitberg2, Adrián Gustavo Turjanski1
1Departamento de Química Biológica/Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, IQUIBICEN/INQUIMAE-UBA/CONICET, Universidad de Buenos Aires, Ciudad Universitaria , Intendente Güiraldes 2160, Pabellón II, Buenos Aires C1428EGA, Argentina.
Journal of the American Chemical Society
|June 28, 2016
概括
内在无序的蛋白质 (IDP) 在与CBP结合时迅速折叠. 这项研究揭示了通过结构化或非结构化过渡状态发生合折叠和结合,调和实验数据.
科学领域:
- 生物化学
- 结构生物学
- 计算生物学
背景情况:
- 内在无序蛋白质 (IDP) 在溶液中缺乏稳定的结构,但在伴侣结合时获得它们.
- 了解IDP的合折叠和结合机制对于破译其功能至关重要.
- 在IDP结合中,过渡状态的性质仍然是实验和计算方法的重大挑战.
研究的目的:
- 研究转录因子c-myb和CREB结合蛋白 (CBP) 之间的结合折叠和结合过程的自由能量场景.
- 阐明绑定机制并描述本模型IDP系统的过渡状态.
- 提供第一个原子分子动力学 (MD) 模拟样本,用于IDP的合折叠和结合的自由能量表面.
主要方法:
- 进行了总计15. 6微秒的原子偏差分子动力学 (MD) 模拟.
- 使用偏差的MD模拟来采样c-myb/CBP相互作用的自由能量表面.
- 在各种结构化和非结构化模型上进行了Go型粗粒度MD模拟.
主要成果:
- 转录因子c- myb在与CBP结合时迅速折叠,没有单一的结合途径.
- 结合过程可以通过具有相似概率的结构化或非结构化过渡状态进行.
- 粗粒模拟表明,合折叠和结合遵循一种本地接触机制.
结论:
- 这些发现与之前关于IDP结合机制的不同实验观察相协调.
- 这项研究表明IDP结合途径是灵活的,可以涉及多种过渡状态类型.
- 提出的原子化MD模拟提供了前所未有的洞察力对内在无序蛋白质的合折叠和结合的动态.
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