Conformational entropy in molecular recognition by proteins
Conformational entropy in molecular recognition by proteins
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DOI：
10.1038/nature05959
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发表时间：
2007-07-19
期刊：
影响因子：
64.8
通讯作者：
Wand, A. Joshua
中科院分区：
文献类型：
--
作者：
Frederick, Kendra King;Marlow, Michael S.;Wand, A. Joshua
蛋白质的分子识别是几乎所有生物过程的基础，特别是细胞信号转导的蛋白质关联。理解蛋白质-蛋白质相互作用的基础需要对它们的关联的热力学进行充分的描述。从历史上看，通过实验估计蛋白质构象熵的变化几乎是不可能的，构象熵是蛋白质结合自由能的一个潜在的重要组成部分。然而，核磁共振波谱已经成为表征蛋白质动力学的有力工具。在这里，我们采用构象动力学的变化作为构象熵相应变化的代理。我们发现钙调蛋白的内部动力学变化在结合多种靶结构域时变化显著。令人惊讶的是，相应构象熵的明显变化与总结合熵的变化呈线性关系。这表明蛋白质构象熵的变化对蛋白质与配体结合的自由能有重要影响。
Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein-protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.