MOLECULAR STRUCTURE OF BIOLOGICAL MOLECULES

我们试图建立几个简单的低聚络合物的结构 使用几种策略的跨膜螺旋，包括组合 的诱变和建模，利用多维异核 核磁共振，也许还有结晶学。同时，我们将使用 序列变异，以探索负责的化学作用 螺旋结构的稳定缔合。使用小角度进行测量 X射线散射法、量热法和电泳法将定义差异。 由于特定的氨基酸取代而产生的稳定性。这些遗嘱 与基于计算建模的预测差异进行比较，通过 能量最小化、分子动力学和模拟退火法。 最初的工作将集中在磷蛋白形成的五聚体上 跨膜螺旋，血糖素螺旋的二聚体，以及 T细胞受体的跨膜片段。结合以下方面的知识 了解其化学原理的结构 形成将导致对结构的改进的预测策略 螺旋膜蛋白。

We seek to establish the structures of several simple oligomeric complexes of transmembrane helices using several strategies, including a combination of mutagenesis and modeling, the use of multi-dimensional heteronuclear NMR, and, perhaps, crystallography. At the same time, we will use sequence variation to probe the chemical interactions responsible for stable association of helical structures. Measurements using small angle x-ray scattering, calorimetry, and electrophoresis will define differences in stability arising from specific amino acid substitutions. These will be compared with predicted differences based on computational modeling via energy minimization, molecular dynamics, and simulated annealing. Initially, work will focus on pentamers formed by phospholamban transmembrane helices, the dimers of glycophorin helices, and transmembrane segments from the T cell receptor. Combining knowledge of the structures with an understanding of the chemical principles of their formation will lead to improved predictive strategies for the structures of helical membrane proteins.