Universality and diversity of the protein folding scenarios: a comprehensive analysis with the aid of a lattice model.
Universality and diversity of the protein folding scenarios: a comprehensive analysis with the aid of a lattice model.
复制标题
蛋白质折叠场景的普遍性和多样性：借助晶格模型的综合分析。
DOI：
10.1016/s1359-0278(96)00019-3
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Shakhnovich,EI
中科院分区：
文献类型：
--
作者：
Mirny,LA;Abkevich,V;Shakhnovich,EI
背景蛋白质折叠中间体的作用一直是一个有很大争议的问题。虽然人们普遍认为，中间体发挥关键作用，最大限度地减少与Levinthal悖论的搜索问题，实验证据已经积累，小蛋白质折叠快，没有任何可检测的intermediates.ResultsWe研究的热力学和动力学折叠使用一个简单的晶格模型。通过设计过程获得的两个折叠序列表现出不同的折叠场景。第一个序列快速折叠到天然状态，并且在折叠期间不显示任何填充的中间体。相比之下，第二个序列折叠得慢得多，经常被困在错误折叠的低能构象。然而，第二序列的一小部分折叠分子在快速轨道上折叠，避免错误折叠的陷阱。在平衡，在相同的温度下，第二个序列有一个高度填充的中间体与结构相似的动力学intermediate.ConclusionOur分析表明，中间体往往可能会破坏本机构象和脱轨的折叠过程中，导致它的陷阱。较少优化的序列通过涉及错误折叠中间体的平行途径折叠。设计得更好的序列在天然状态下更稳定，并且在双态过程中快速折叠而没有中间体。
BackgoundThe role of intermediates in protein folding has been a matter of great controversy. Although it was widely believed that intermediates play a key role in minimizing the search problem associated with the Levinthal paradox, experimental evidence has been accumulating that small proteins fold fast without any detectable intermediates.ResultsWe study the thermodynamics and kinetics of folding using a simple lattice model. Two folding sequences obtained by the design procedure exhibit different folding scenarios. The first sequence folds fast to the native state and does not exhibit any populated intermediates during folding. In contrast, the second sequence folds much slower, often being trapped in misfolded low-energy conformations. However, a small fraction of folding molecules for the second sequence fold on a fast track avoiding misfolded traps. In equilibrium at the same temperature the second sequence has a highly populated intermediate with structure similar to that of the kinetics intermediate.ConclusionOur analysis suggests that intermediates may often destabilize native conformations and derail the folding process leading it to traps. Less-optimized sequences fold via parallel pathways involving misfolded intermediates. A better designed sequence is more stable in the native state and folds fast without intermediates in a two-state process.