Frederick Kendra King, Marlow Michael S, Valentine Kathleen G, Wand A Joshua
Johnson Research Foundation and Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature. 2007 Jul 19;448(7151):325-9. doi: 10.1038/nature05959.
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.
蛋白质的分子识别几乎是所有生物过程的基础，尤其是细胞信号转导所依赖的蛋白质相互作用。理解蛋白质 - 蛋白质相互作用的基础需要全面表征其结合的热力学性质。从历史上看，实际上不可能通过实验估计蛋白质构象熵的变化，而构象熵可能是蛋白质结合自由能的一个重要组成部分。然而，核磁共振光谱已成为表征蛋白质动力学的强大工具。在这里，我们将构象动力学的变化用作构象熵相应变化的替代指标。我们发现，钙调蛋白在结合各种靶结构域时，其内部动力学变化显著。令人惊讶的是，相应构象熵的表观变化与整体结合熵的变化呈线性相关。这表明蛋白质构象熵的变化可对蛋白质 - 配体结合自由能有显著贡献。
