Binding Energetics and Dynamic Processes in Protein Dimers

生物专一性的本质在于蛋白质-配体复合体的能量学、动力学和结构方面。虽然人们非常重视阐明蛋白质的结构方面，主要是通过X射线衍射研究，但如果没有系统的能量学和动力学知识，就不能理解配体结合和酶催化。在过去的十年里，核磁共振、氢交换和荧光光谱等各种技术证明了蛋白质是动态的分子。分子动力学计算等理论处理也预测了一些蛋白质残基的运动。这样就形成了一幅蛋白质分子的图像，这与早期X射线衍射研究所建议的僵硬、静态的描述截然不同。目前，人们正致力于阐明这些运动对酶催化和配基结合的能量学的功能意义。Jameson博士将使用荧光光谱、升高的静水压力和酶动力学测量来研究苹果酸脱氢酶、细胞质苹果酸脱氢酶和延伸因子中的配体结合和亚单位-亚单位之间的相互作用。荧光光谱学允许根据环境和蛋白质中色氨酸的旋转动力学来确定寿命。高压技术正变得越来越多地应用于生物分子，因为与温度效应相比，该技术具有固有的优势。

The essence of biological specificity resides in the energetics, dynamics and structural aspects of protein-ligand complexes. Although a great deal of emphasis has been placed upon elucidation of the structural aspects of proteins, primarily through the use of X-ray diffraction studies, the understanding of ligand binding and enzyme catalysis cannot proceed in the absence of knowledge of the energetics and dynamics of the systems. During the past decade diverse techniques such as NMR, hydrogen exchange and fluorescence spectroscopy have demonstrated that proteins are dynamic molecules. Theoretical treatments such as molecular dynamics calculations have also predicted motions of some proteins residues. A picture of the protein molecule has thus developed which is quite different from the rigid, static descriptions suggested by earlier X-ray diffraction studies. Considerable effort is now being focused on elucidating the functional significance of these motions to enzyme catalysis and the energetics of ligand binding. Dr. Jameson will examine ligand binding and subunit-subunit interactions in malate dehydrogenase, cytoplasmic malate dehydrogenase and elongation factor using fluorescence spectroscopy, elevated hydrostatic pressure and enzyme kinetic measurements. Fluorescence spectroscopy permits the determination of lifetimes as a function of environment and rotation dynamics of tryptophans in proteins. High pressure techniques are becoming more applied to biological molecules because of the intrinsic advantages of the technique compared to temperature effects.