Chan Hue Sun, Zhang Zhuqing, Wallin Stefan, Liu Zhirong
Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Annu Rev Phys Chem. 2011;62:301-26. doi: 10.1146/annurev-physchem-032210-103405.
Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins.
粗粒度、自包含的聚合物模型是蛋白质折叠研究中的强大工具。它们对于评估来自缺乏明确链表示的不太严格的理论方法的预测也至关重要。在这里，我们回顾了协同蛋白质折叠粗粒度建模的进展，特别指出莱文塔尔悖论是针对20世纪60年代末类似两态折叠的实验发现而提出的，而不是针对构象搜索本身的问题。理论与实验之间的比较表明，去溶剂化障碍在协同折叠中起着重要作用，这可能通常源于局部构象偏好与非局部堆积相互作用之间的耦合。许多这些原理已通过以天然态为中心的模型得到阐明，其中非天然相互作用可以微扰方式处理。我们讨论了这些进展以及粗粒度链建模在打结蛋白质和内在无序蛋白质方面的最新应用。
