Scaling behavior and structure of denatured proteins
Scaling behavior and structure of denatured proteins
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DOI：
10.1016/j.str.2005.04.009
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发表时间：
2005-07-01
期刊：
影响因子：
5.7
通讯作者：
Dokholyan, NV
中科院分区：
文献类型：
--
作者：
Ding, F;Jha, RK;Dokholyan, NV
没有固定结构的随机线圈构象集合长期以来被认为是变性蛋白质的经典模型，因为它与实验确定的蛋白质大小的缩放一致。然而，最近对高化学变性剂浓度下蛋白质的核磁共振波谱研究表明，与经典的随机线圈图相反，存在大量的天然类结构。为了调和这些看似有争议的观察结果，我们通过分子动力学模拟来研究实验表征的蛋白质的热变性状态。对于所有研究的蛋白质，我们发现变性状态确实对天然状态有很强的局部构象偏差，而蛋白质大小的随机线圈幂律缩放则被保留。此外，我们解释了为什么实验确定的蛋白肌酸激酶的大小不遵循一般缩放。在模拟中，我们观察到该蛋白表现出稳定的中间状态，其大小与报道的实验观察一致。
An ensemble of random-coil conformations with no persistent structures has long been accepted as the classical model of denatured proteins due to its consistency with the experimentally determined scaling of protein sizes. However, recent NMR spectroscopy studies on proteins at high chemical denaturant concentrations suggest the presence of significant amounts of native-like structures, in contrast to the classical random-coil picture. To reconcile these seemingly controversial observations, we examine thermally denatured states of experimentally characterized proteins by using molecular dynamics simulations. For all studied proteins, we find that denatured states indeed have strong local conformational bias toward native states while a random-coil power law scaling of protein sizes is preserved. In addition, we explain why experimentally determined size of the protein creatine kinase does not follow general scaling. In simulations, we observe that this protein exhibits a stable intermediate state, the size of which is consistent with the reported experimental observation.