Structures and relative free energies of partially folded states of proteins
Structures and relative free energies of partially folded states of proteins
复制标题
蛋白质部分折叠状态的结构和相对自由能
DOI：
10.1073/pnas.2036516100
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发表时间：
2003
影响因子：
11.1
通讯作者：
C. Dobson
中科院分区：
文献类型：
--
作者：
M. Vendruscolo;E. Paci;M. Karplus;C. Dobson
蛋白质折叠成明确紧凑结构的能力是自然选择对生物分子影响的最显著例子之一。为了了解它们的性质，包括稳定性、折叠机制、错误折叠和结合的可能性，有必要了解蛋白质的自由能景观。我们使用核磁共振数据作为蒙特卡罗采样程序的约束，以确定在尿素浓度增加的情况下，由人α-乳清蛋白填充的结构的集合。代表蛋白质部分折叠状态的结构集合表明，两个结构核心，对应于天然蛋白的部分α和β结构域，即使在定义其存在的天然相互作用被大大削弱时也被保留下来。对残余接触网络的分析揭示了两个结构核心之间存在一个复杂的界面区域，并表明在该界面内特定相互作用的发展是实现原生结构的关键步骤。利用核磁共振数据确定的构象的相对概率，构建了无尿素条件下α-乳清蛋白的粗粒度自由能图。景观的形式，以及不同核心的存在，支持了坚固性和模块化的概念，这些特性使复杂蛋白质的折叠成为可能。
The ability of proteins to fold to well defined compact structures is one of the most remarkable examples of the effect of natural selection on biological molecules. To understand their properties, including the stability, the mechanism of folding, and the possibilities of misfolding and association, it is necessary to know the protein free energy landscape. We use NMR data as restraints in a Monte Carlo sampling procedure to determine the ensemble of structures populated by human α-lactalbumin in the presence of increasing concentrations of urea. The ensembles of structures that represent the partially folded states of the protein show that two structural cores, corresponding to portions of the α and β domains of the native protein, are preserved even when the native-like interactions that define their existence are substantially weakened. Analysis of the network of residual contacts reveals the presence of a complex interface region between the two structural cores and indicates that the development of specific interactions within this interface is the key step in achieving the native structure. The relative probabilities of the conformations determined from the NMR data are used to construct a coarse-grained free energy landscape for α-lactalbumin in the absence of urea. The form of the landscape, together with the existence of distinct cores, supports the concept that robustness and modularity are the properties that make possible the folding of complex proteins.
28-111二硫键限制了α-乳清蛋白熔球，削弱了其折叠协同性。
DOI：
10.1073/pnas.96.20.11283
发表时间：
1999
影响因子：
11.1
作者：
Luo,Y;Baldwin,RL
通讯作者：
Baldwin,RL
影响因子：
5.6
作者：
Day, R;Bennion, BJ;Daggett, V
通讯作者：
Daggett, V