CAREER: Controlling Helix-Helix Interactions in Membrane Proteins

这个研究项目解决了膜蛋白中的螺旋-螺旋相互作用。与水溶剂和烃溶剂相分离的材料将用于指导膜双层内螺旋的填充和组装。肽与氟化或p-氨基苯丙氨酸残基内衬螺旋间的表面，并配备了烃侧链在膜暴露的位置将被用来调查驱动力，包装的趋势，和膜内的组件的取向。使用选定的非天然氨基酸的组合，侧链性质和自组装之间的关系将被探索。生物物理学研究，详细说明分区和折叠的热力学将进行，以获得肽-脂质相互作用的详细地图。在洗涤剂存在下的沉降平衡和荧光共振能量转移将用于确定组装物的分子量和化学计量。将采用扫描力显微镜直接观察形态学变化。将实施各种旨在为学习环境带来互动的课程改革，并将启动以科学和政策研讨会为形式的面向非科学家的公共宣传计划。在有机和高分子化学计划的职业奖的支持下，塔夫茨大学化学系的Krishna Kumar教授，正在进行与蛋白质的设计聚集有关的基础研究。通过开发新的方法来控制肽分子如何相互作用，Kumar教授的研究可能会导致新的方法来控制分子通过膜和新的药物输送系统。库马尔教授将通过一个公开的研讨会计划，解决科学和科学政策的非科学家带来科学，并将通过一系列互动学习项目的发展，提高本科生的教育经验。

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.