Simultaneous determination of protein structure and dynamics
Simultaneous determination of protein structure and dynamics
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DOI：
10.1038/nature03199
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发表时间：
2005-01-13
期刊：
影响因子：
64.8
通讯作者：
Vendruscolo, M
中科院分区：
文献类型：
--
作者：
Lindorff-Larsen, K;Best, RB;Vendruscolo, M
我们提出了一个协议的实验测定合奏的蛋白质构象，同时代表天然结构及其相关的动力学。该程序结合了核磁共振光谱的优势-在原子水平上获得有关蛋白质的结构和动力学特征的实验信息-与分子动力学模拟的能力，以探索广泛的蛋白质构象。我们说明了在溶液中的人泛素的方法，并发现有相当大的构象异质性，整个蛋白质结构。蛋白质的内部原子紧密地堆积在每个单独的构象中，这有助于整体，但它们的整体行为可以被描述为具有显著程度的液体状特征。该协议是完全通用的，应该导致我们理解和利用天然蛋白质结构的能力的重大进展。
We present a protocol for the experimental determination of ensembles of protein conformations that represent simultaneously the native structure and its associated dynamics. The procedure combines the strengths of nuclear magnetic resonance spectroscopy-for obtaining experimental information at the atomic level about the structural and dynamical features of proteins-with the ability of molecular dynamics simulations to explore a wide range of protein conformations. We illustrate the method for human ubiquitin in solution and find that there is considerable conformational heterogeneity throughout the protein structure. The interior atoms of the protein are tightly packed in each individual conformation that contributes to the ensemble but their overall behaviour can be described as having a significant degree of liquid-like character. The protocol is completely general and should lead to significant advances in our ability to understand and utilize the structures of native proteins.