Itoh Kazuhito, Sasai Masaki
Department of Complex Systems Science, Graduate School of Information Science, Graduate School of Engineering, Nagoya University, Nagoya 464-8601, Japan.
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7298-303. doi: 10.1073/pnas.0510324103. Epub 2006 Apr 28.
The folding pathway of the B domain of protein A is the pathway most intensively studied by computer simulations. Recent systematic measurement of Phi values by Sato et al., however, has shown that none of the published computational predictions is consistent with the detailed features of the experimentally observed folding mechanism. In this article we use a statistical mechanical model of folding to show that sensitive dependence of multiple transition state ensembles on temperature and the denaturant concentration is the key to resolving the inconsistency among simulations and the experiment. Such sensitivity in multiple transition state ensembles is a natural consequence of symmetry-breaking in a nearly symmetrical protein.
蛋白A的B结构域的折叠途径是计算机模拟研究最为深入的途径。然而,佐藤等人最近对Phi值进行的系统测量表明,已发表的计算预测结果均与实验观察到的折叠机制的详细特征不一致。在本文中,我们使用一种折叠的统计力学模型来表明,多个过渡态系综对温度和变性剂浓度的敏感依赖性是解决模拟与实验之间不一致问题的关键。多个过渡态系综中的这种敏感性是近乎对称的蛋白质中对称性破缺的自然结果。