Thermodynamics of Structural Fluctuations in Proteins

蛋白质结构波动的生物学作用尚未确定，尽管它们的存在已被充分证明。这在一定程度上是由于对这一现象的热力学基础的不确定性。可能的范围从定义的构象底物之间的通道，如在血红蛋白的变构模型中，到沿着酶底物复合体的反应坐标的通道的纯动力学调节。罗森博格博士将以他为这些现象开发的物理模型为基础，进行计划中的研究。总的目标将是测试模型的有效性，然后证明它在解释生物过程中结构波动的可能功能方面的有效性。他选择了可靠的实验系统，使用了表征良好的蛋白质，并测试了分析方法。这个项目的一个主要优点是用于研究蛋白质运动的方法(氢交换、荧光猝灭、热稳定性)的多样性。

The biological role of structural fluctuations in proteins has not been established although their presence has been amply demonstrated. This is partly due to uncertainty about the thermodynamic basis for the phenomenon. Possibilities range from passage between defined conformational substrates, as in the allosteric model for hemoglobin, to pure kinetic regulation of the passage along the reaction coordinate of enzyme substrate complex. Dr. Rosenberg will base the planned research on a physical model that he has developed for these phenomena. The overall goal will be to test the validity of model and then demonstrate its usefulness in explaining the possible function of structural fluctuations in biological processes. He has selected sound experimental systems using well- characterized proteins and tested analytical methodologies. A major strength of this project is the diversity of methodologies (hydrogen-exchange, fluorescence-quenching, thermal stability) being applied to the study of protein motions.