CAREER: Controlling Helix-Helix Interactions in Membrane Proteins

这项研究计划解决了膜蛋白中螺旋-螺旋的相互作用。相分离于水和碳氢溶剂的材料将被用来指导螺旋体在膜双层内的填充和组装。带有氟化或对氨基苯丙氨酸残基的多肽排列在螺旋间表面，并在膜暴露位置配备碳氢侧链，将用于研究膜内组件的驱动力、堆积趋势和取向。使用选择的非天然氨基酸的组合，将探索侧链特性和自组装之间的关系。将进行详细的生物物理研究，详细说明分配和折叠的热力学，以获得肽-脂相互作用的详细图谱。在洗涤剂存在的情况下，将使用沉淀平衡和荧光共振能量转移来确定组件的相对分子质量和化学计量。扫描力显微镜将被用来直接观察形态变化。将实施旨在为学习环境带来互动性的各种课程改革，并将启动一项以科学和政策研讨会的形式针对非科学家的公共外展计划。在有机和高分子化学计划的这一职业奖的支持下，塔夫茨大学化学系的Krishna Kumar教授正在开展与蛋白质聚集设计相关的基础研究。通过开发新的方法来控制多肽分子之间的相互作用，库马尔教授的研究可能会带来控制分子跨膜通道和新的药物输送系统的新方法。库马尔教授将通过一个讨论科学和科学政策的公共研讨会项目将科学带给非科学家，并将通过开发一系列互动学习项目来增强本科生的教育体验。

This research program addresses helix-helix interactions in membrane proteins. Materials that phase separate from both aqueous and hydrocarbon solvents will be utilized to direct the packing and assembly of helices within membrane bilayers. Peptides with fluorinated or p-aminophenylalanine residues lining interhelical surfaces and equipped with hydrocarbon sidechains at membrane exposed positions will be used to investigate driving force, packing tendencies, and orientation of the assemblies within the membrane. Using a combination of selected unnatural amino acids, the relationship between sidechain properties and self-assembly will be explored. Biophysical studies detailing the thermodynamics of partitioning and folding will be carried out to obtain a detailed map of peptide-lipid interactions. Sedimentation equilibrium and fluorescence resonance energy transfer in the presence of detergents will be used to ascertain the molecular weight and stoichiometries of the assemblies. Scanning force microscopy will be employed for direct visualization of morphological changes. A variety of curricular changes designed to bring interactivity to the learning environment will be implemented, and a public outreach program in the form of science and policy seminars targeting the non-scientist will be initiated.With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Krishna Kumar, of the Department of Chemistry at Tufts University, is carrying out fundamental studies related to the designed aggregation of proteins. By developing new approaches for the control of how peptide molecules interact with one-another, Professor Kumar's studies may lead to new methods to control the passage of molecules across membranes and to new drug delivery systems. Professor Kumar will bring science to the non-scientist through a public seminar program addressing both science and science policy and will enhance the educational experience of undergraduates through the development of a series of interactive learning projects.