Chen Tao, Song Jianhui, Chan Hue Sun
Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7, Canada.
Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7, Canada.
Curr Opin Struct Biol. 2015 Feb;30:32-42. doi: 10.1016/j.sbi.2014.12.002. Epub 2014 Dec 24.
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.
内在无序蛋白质（IDP）多样的生物学功能显著提升了我们对蛋白质构象多样性的认识，而能量有利但功能有害的非天然相互作用的存在凸显了进化优化的物理局限性。在此，我们综述了利用生物物理建模深入了解实验观察到的非天然行为和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，其遵循的组织原则与单体球状蛋白质协同折叠中的局部-非局部耦合机制基本相同。相比之下，对于概念新颖但研究较少的“模糊”复合物，其中功能结合的IDP在很大程度上仍保持无序状态，需要更具创新性的静电和芳香族相互作用理论。
