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Published on: April 10, 2012
一个蛋白质体球的原生组合和折叠:下坡折叠的功能后果
Athi N Naganathan1, Modesto Orozco
1IRB-BSC Joint Research Program in Computational Biology, Barcelona Supercomputing Center, Torre Girona, C/Jordi Girona 31, Barcelona 08034, Spain. anarayan@bsc.es
Journal of the American Chemical Society
|July 8, 2011
概括
蛋白质的内在障碍和灵活性挑战了传统的结构-功能范式. 这项研究揭示了像NCBD这样的化球状蛋白质利用下坡折叠和结构灵活性进行广泛的伴侣结合,挑战了已有的蛋白质折叠模型.
科学领域:
- 蛋白质折叠的动态 蛋白质折叠的动态
- 本质上无序的蛋白质的生物物理学.
- 计算结构生物学计算结构生物学
背景情况:
- 传统的蛋白质观点认为,固定的结构决定了功能,但越来越多地认识到内在的混乱和灵活性.
- 融球状 (MG) 蛋白质,具有二次结构但流体核心,具有挑战性的实验和计算研究.
- 了解MG蛋白折叠对于阐明它们的功能作用和结合乱交至关重要.
研究的目的:
- 为了研究α-螺旋状型球状蛋白 NCBD.的折叠机制.
- 为了描述NCBD化球体状态的原生组合.
- 探索NCBD下坡折叠,形状灵活性和约束性乱交之间的联系.
主要方法:
- 使用了三种不同的计算方法:统计机械变量屏障模型,基于C(α的Gō模型和全原子分子动力学 (MD) 模拟.
- 为化球体状态生成了一个受约束但异质的本地合奏.
- 与实验数据对比验证的模拟结果,包括SAXS,CD和NMR.
主要成果:
- NCBD表现出一个不稳定的,单一国家的下坡文件的特征.
- 通过计算生成了NCBD化球体的异质原生组合,与实验数据一致.
- 本地合奏支持结合多个伴侣的形状选择.
- 下坡折叠与NCBD进化选择的结构灵活性和约束性乱交直接相关.
结论:
- NCBD的折叠机制涉及下坡折叠和显著的形状灵活性,使广泛的合作伙伴具有约束力.
- 这项研究提供了第一个基于模拟的限制性,异构的化球体本土集体的表征.
- 采用的多模型方法对于研究蛋白质折叠机制和化球体热力学是有效的.
- 化球体的热力学特征与小单域蛋白质的折叠机制的光谱一致.
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The...
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Molecular Chaperones and Protein Folding
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