MOLECULAR STRUCTURE OF BIOLOGICAL MOLECULES

我们试图建立几个简单的低聚复合物的结构 使用几种策略，包括组合 诱变和建模，使用多维异质性 核磁共振，也许还有结晶学。 同时，我们将利用 序列变异来探测化学相互作用， 螺旋结构的稳定结合。使用小角度测量 X射线散射、量热法和电泳法将确定差异 由特定氨基酸取代引起的稳定性。 这些将 与基于计算建模的预测差异进行比较， 能量最小化、分子动力学和模拟退火。 最初，工作将集中在受磷蛋白形成的五聚体上 跨膜螺旋，血型糖蛋白螺旋的二聚体，和 T细胞受体的跨膜片段。 结合知识， 了解其结构的化学原理， 形成将导致改进的预测战略的结构 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.