Clementi C, Nymeyer H, Onuchic J N
Department of Physics, University of California at San Diego, La Jolla, CA 92093-0319, USA.
J Mol Biol. 2000 May 19;298(5):937-53. doi: 10.1006/jmbi.2000.3693.
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 Go-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.
最近的实验结果表明，天然折叠或拓扑结构在决定过渡态集合的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这样。为了研究折叠过程中拓扑控制的程度，我们使用类Go势构建了五个小球状蛋白质的简化模型，以保留有关天然结构的信息，但大幅减少残基-残基天然相互作用之间的能量挫折和能量异质性，进而研究了这些模型的折叠情况。通过比较过渡态集合（通过Phi值实验确定）和中间体的结构与使用我们的模型获得的结构，我们表明，至少对于所分析的蛋白质，这些能量上无挫折的模型可以重现过渡态集合和“途中”中间体的全局实验已知特征。这一结果清楚地表明，只要蛋白质序列的能量挫折足够小，拓扑结构在决定折叠机制中就起着核心作用。
