STRUCTURAL & ENERGETIC PRINCIPLES OF MEMBRANE PROTEINS

描述（改编自摘要）：理解结构能量学 膜蛋白远远落后于可溶性蛋白。这部分是 这是因为在原子分辨率下已知的膜蛋白结构很少。 然而，同样负责的是缺乏定量的热力学 关于膜蛋白折叠和组装的信息。 拟议的工作将提供有关特异性的数据， 膜蛋白中螺旋-螺旋缔合的稳定性。实验 方法将产生一个详细的结构和热力学分析， 血型糖蛋白跨膜结构域二聚体。新的热力学测量， 超离心将允许对序列进行定量评估 二聚体稳定性依赖于许多位点特异性突变体。结构 在相同突变体的洗涤剂胶束中通过溶液NMR的测定将 提供了一个结构框架，在此基础上， 观察到对单体二聚体平衡的影响。这些原则来自于 结构和热力学测量的整合将是 结合到现有的计算算法中，以提高其 在膜蛋白的建模、预测和设计方面的表现。

DESCRIPTION (Adapted from abstract): Understanding of structural energetics of membrane proteins lags far behind that of soluble proteins. In part, this is due to the rarity of membrane protein structures known at atomic resolution. Equally responsible, however, is the lack of quantitative thermodynamic information on membrane protein folding and assembly. The work being proposed will provide data concerning the specificity and stability of helix-helix associations in membrane proteins. The experimental approach will produce a detailed structural and thermodynamic analysis of the glycophorin transmembrane domain dimer. Novel thermodynamic measurements using ultracentrifugation will permit a quantitative assessment of the sequence dependence of dimer stability through numerous site specific mutants. Structure determination by solution NMR in detergent micelles of the same mutants will provide a structural framework on which to understand the experimentally observed effects on the monomer dimer equilibrium. Principles that emerge from the integration of the structural and thermodynamic measurements will be incorporated into existing computational algorithms to improve their performance in modeling, prediction, and design efforts for membrane proteins.