内部摩擦对折叠机制的依赖性
Wenwei Zheng1, David De Sancho, Travis Hoppe
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
Journal of the American Chemical Society
|February 28, 2015
概括
蛋白质折叠中的内部摩擦是由能量屏障附近的扭转角度变化引起的,特别是在螺旋形成过程中. 这解释了为什么蛋白质和折叠路径之间的摩擦变化.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 蛋白质动力学 蛋白质动力学
背景情况:
- 内部摩擦,观察到粘度依赖的折叠速率,是蛋白质折叠动态的一个关键方面.
- 以前的模拟表明扭力屏障的穿越会导致内部摩擦,但这种变化仍然无法解释.
研究的目的:
- 为了阐明蛋白质折叠中内部摩擦的分子起源.
- 解释内部摩擦中的蛋白质特异性和路径依赖的变化.
主要方法:
- 全原子分子动力学模拟与不同的溶剂粘度.
- 过渡路径采样以确定折叠反应速率.
- 分析折叠动态的马尔科夫状态模型.
主要成果:
- 与发针形成相比,在涉及螺旋形成的折叠路径中,内部摩擦显著更高.
- 在折叠的自由能量屏障附近扭矩角度的重新排列被确定为内部摩擦的来源.
- 模拟结果与粘度依赖的实验观测结果一致.
结论:
- 蛋白质折叠中的内部摩擦与在穿越屏障时需要显著扭转角度变化的必要性有机械联系.
- 这为不同蛋白质和折叠景观内部摩擦的异质性提供了分子解释.
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