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

被引:1033
作者
Clementi, C [1 ]
Nymeyer, H [1 ]
Onuchic, JN [1 ]
机构
[1] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA
关键词
protein folding; transition state; folding intermediate; Phi-value analysis; molecular dynamics simulations;
D O I
10.1006/jmbi.2000.3693
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:937 / 953
页数:17
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