Theoretical perspectives on nonnative interactions and intrinsic disorder in protein folding and binding
Theoretical perspectives on nonnative interactions and intrinsic disorder in protein folding and binding
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DOI：
10.1016/j.sbi.2014.12.002
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发表时间：
2015-02-01
影响因子：
6.8
通讯作者：
Chan, Hue Sun
中科院分区：
文献类型：
--
作者：
Chen, Tao;Song, Jianhui;Chan, Hue Sun
本质上无序蛋白质（IDP）的多样化生物学功能显着提高了我们对蛋白质构象多功能性的认识，而能量上有利但功能上有害的非天然相互作用的存在强调了进化优化的物理局限性。在这里，我们调查了使用生物物理模型来深入了解实验观察到的非本地行为和 IDP 特性的最新进展。迄今为止，IDP 相互作用的模拟主要集中在耦合折叠结合上，其基本上遵循与单体球状蛋白协同折叠中的局部-非局部耦合机制相同的组织原理。相比之下，对于概念上新颖但较少探索的“模糊”复合物，需要更多创新的静电和芳香相互作用理论，其中功能结合的IDP在很大程度上仍然是无序的。
The diverse biological functions of intrinsically disordered proteins (IDPs) have markedly raised our appreciation of protein conformational versatility, whereas the existence of energetically favorable yet functional detrimental nonnative interactions underscores the physical limitations of evolutionary optimization. Here we survey recent advances in using biophysical modeling to gain insight into experimentally observed nonnative behaviors and IDP properties. Simulations of IDP interactions to date focus mostly on coupled folding-binding, which follows essentially the same organizing principle as the local-nonlocal coupling mechanism in cooperative folding of monomeric globular proteins. By contrast, more innovative theories of electrostatic and aromatic interactions are needed for the conceptually novel but less-explored 'fuzzy' complexes in which the functionally bound IDPs remain largely disordered.