Topological and energetic factors: What determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins
Topological and energetic factors: What determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins
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DOI：
10.1006/jmbi.2000.3693
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发表时间：
2000-05-19
影响因子：
5.6
通讯作者：
Onuchic, JN
中科院分区：
文献类型：
--
作者：
Clementi, C;Nymeyer, H;Onuchic, JN
最近的实验结果表明，原生折叠或拓扑结构在决定过渡态集合结构方面起着主要作用，至少对于小的、快速折叠的蛋白质是如此。为了研究折叠过程的拓扑控制程度，我们研究了五种小球状蛋白质的折叠简化模型，这些模型使用G (o) over bar-样电位构建，以保留有关天然结构的信息，但大大减少残基-残基天然相互作用之间的能量挫折和能量异质性。通过比较过渡态系综（实验上由ph值确定）和中间体的结构与我们的模型得到的结构，我们表明，这些能量不受挫折的模型可以重现实验上已知的过渡态系综和“途中”中间体的整体特征，至少对于所分析的蛋白质是这样。这一结果清楚地表明，只要蛋白质序列受到的干扰足够小，拓扑结构在确定折叠机制方面起着核心作用。(C) 2000年学术出版社。
Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small, fast-folding proteins. To investigate the extent of the topological control of the folding process, we studied the folding of simplified models of five small globular proteins constructed using a G (o) over bar-like potential to retain the information about the native structures but drastically reduce the energetic frustration and energetic heterogeneity among residue-residue native interactions. By comparing the structure of the transition state ensemble (experimentally determined by Phi-values) and of the intermediates with those obtained using our models, we show that these energetically unfrustrated models can reproduce the global experimentally known features of the transition state ensembles and "en-route" intermediates, at least for the analyzed proteins. This result clearly indicates that, as long as the protein sequence is sufficiently minimally frustrated, topology plays a central role in determining the folding mechanism. (C) 2000 Academic Press.