Departments of Biology and Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
Biophys Chem. 2011 Nov;159(1):129-41. doi: 10.1016/j.bpc.2011.05.020. Epub 2011 May 31.
It is now well-known that proteins exist at equilibrium as ensembles of conformational states rather than as unique static structures. Here we review from an ensemble perspective important biological effects of such spontaneous fluctuations on protein allostery, function, and evolution. However, rather than present a thorough literature review on each subject, we focus instead on connecting these phenomena through the ensemble-based experimental, theoretical, and computational investigations from our laboratory over the past decade. Special emphasis is given to insights that run counter to some of the prevailing ideas that have emerged over the past 40 years of structural biology research. For instance, when proteins are viewed as conformational ensembles rather than as single structures, the commonly held notion of an allosteric pathway as an obligate series of individual structural distortions loses its meaning. Instead, allostery can result from energetic linkage between distal sites as one Boltzmann distribution of states transitions to another. Additionally, the emerging principles from this ensemble view of proteins have proven surprisingly useful in describing the role of intrinsic disorder in inter-domain communication, functional adaptation mediated by mutational control of fluctuations, and evolutionary conservation of the energetics of protein stability.
现在大家都知道，蛋白质以构象状态的平衡集合体而不是独特的静态结构存在。在这里，我们从集合的角度回顾了这种自发波动对蛋白质变构、功能和进化的重要生物学影响。然而，我们并没有对每个主题进行全面的文献综述，而是专注于通过过去十年我们实验室基于集合的实验、理论和计算研究将这些现象联系起来。特别强调的是，与过去 40 年结构生物学研究中出现的一些流行观点相悖的观点。例如，当蛋白质被视为构象集合体而不是单个结构时，变构途径作为一系列必需的单个结构扭曲的概念就失去了意义。相反，变构可以由远距离位点之间的能量联系引起，当一个玻尔兹曼态分布跃迁到另一个态分布时。此外，从蛋白质集合的角度得出的这些新原则在描述固有无序在域间通讯中的作用、通过突变控制波动进行功能适应以及蛋白质稳定性的能量的进化保守性方面非常有用。
