Direct molecular dynamics observation of protein folding transition state ensemble
Direct molecular dynamics observation of protein folding transition state ensemble
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DOI：
10.1016/s0006-3495(02)75352-6
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发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
Shakhnovich, EI
中科院分区：
文献类型：
--
作者：
Ding, F;Dokholyan, NV;Shakhnovich, EI
蛋白质过渡态系综（TSE）是一组有50%的可能性快速转化为折叠态，50%的可能性快速展开的构象，它的概念构成了蛋白质工程实验的现代解释的基础。已经证实，在许多蛋白质中构成TSE的构象是围绕特定折叠核构建的天然状态的扩展和扭曲形式。这一观点得到了一些格上和非格上模拟的支持。在这里，我们报告了直接观察和表征的TSE的分子动态折叠模拟的C-Src SH 3结构域，一个小的蛋白质，已被广泛研究的实验。我们的分析揭示了一组关键的残基之间的相互作用，保守的进化，必须形成进入动力学盆地的吸引力的天然状态。
The concept of the protein transition state ensemble (TSE), a collection of the conformations that have 50% probability to convert rapidly to the folded state and 50% chance to rapidly unfold, constitutes the basis of the modern interpretation of protein engineering experiments. It has been conjectured that conformations constituting the TSE in many proteins are the expanded and distorted forms of the native state built around a specific folding nucleus. This view has been supported by a number of on-lattice and off-lattice simulations. Here we report a direct observation and characterization of the TSE by molecular dynamic folding simulations of the C-Src SH3 domain, a small protein that has been extensively studied experimentally. Our analysis reveals a set of key interactions between residues, conserved by evolution, that must be formed to enter the kinetic basin of attraction of the native state.