Differential refractometer and SAXS

伴随着结构生物学的快速发展，在蛋白质相互作用和蛋白质稳定性和折叠的分子力方面定义了生物化学功能和机制。蛋白质结构的知识并不能确保准确预测功能和生物活性。为了充分表征底物、其他蛋白质或配体（如底物、核酸、小分子配体或离子）的蛋白质结合中的特定生物分子相互作用，对蛋白质相互作用中的驱动力的分子理解需要了解许多不同的参数。热力学提供了驱动生物分子相互作用的能量力的信息。这种对催化、结合和稳定过程的理解可以用来解决疾病途径的复杂过程，并制定防治疾病的战略。这类策略最常见的例子是根据新药与特定酶或调节蛋白结合的可能性来设计新药。此外，正在设计干扰或刺激人类和动物体内代谢途径的新药，以改善引起疾病症状的异常生化过程。申请人实验室的研究集中在理解与催化周转相关的亚基间信号传导、嗜极古细菌蛋白的蛋白质稳定性、蛋白质-核酸识别以及叶绿素生物合成中的关键酶GSAM的稳定性和结合特性。 现代生物化学实验室专注于蛋白质结构-功能关系的研究，结合了许多技术，将从蛋白质结构测定到目标系统的生物化学和生物物理表征的步骤整合在一起。本申请中要求的设备是该策略的组成部分，包括用于非常精确的蛋白质和配体浓度测定的差示折射计，以及用于现有内部小角X射线散射（SAXS）设施的比色皿样品更换器，以分析生物分子相互作用的热力学参数，从而研究蛋白质结合和蛋白质稳定性的分子细节。

Accompanying the rapid advances in structural biology is the definition of biochemical function and mechanism in terms of molecular forces in protein interactions and protein stability and folding. Knowledge of protein structure does not ensure accurate prediction of function and biological activity. To fully characterize specific biomolecular interactions in protein binding of substrates, other proteins or ligands such as substrates, nucleic acids, small molecule ligands or ions, a molecular understanding of driving forces in protein interactions requires knowledge of a number of different parameters. Thermodynamics provides information on the energetic forces that drive biomolecular interactions. This understanding of catalytic, binding and stability processes can then be exploited to tackle the complex processes underlying disease pathways and to devise strategies for combating diseases. The most common example of such strategies is the design of new drugs based on the likelihood of their binding to specific enzymes or regulatory proteins. In addition, new drugs are being designed that either interfere with or stimulate metabolic pathways within humans and animals to ameliorate aberrant biochemical processes causing disease symptoms. Research in the laboratory of the applicant is focused on understanding intersubunit signaling linked to catalytic turnover, protein stability of extremophilic archea proteins, protein-nucleic acid recognition, and stability and binding properties of GSAM, a key enzyme in chlorophyll biosynthesis. A modern biochemistry laboratory focused on protein study of structure-function relationships combines a number of technologies to integrate the steps from protein structure determination to biochemical and biophysical characterization of the target systems. The equipment requested in this application is integral to this strategy and includes a differential refractometer for very precise protein and ligand concentration determinations, and a Cuvette Sample Changer for an existing in-house Small-Angle X-Ray Scattering (SAXS) facility to analyze thermodynamic parameters of biomolecular interactions to study molecular details of protein binding and protein stability.