Structure determination by vibrational spectroscopy

描述（由申请人提供）：这是一项将联合收割机二维红外光谱与氧化足迹/质谱和分子力学模拟相结合以回答关于淀粉样β蛋白原纤维形成和结构的关键问题的提议。有两个具体目标：1。淀粉样纤维的相关结构和形态。2.描述A？的低聚形式的结构发展。 这个项目是一个跨学科的合作，一个医生，药理学家调查阿尔茨海默病的病理学，和化学物理学家开拓新的光谱方法。我们将首次应用一种新兴的，强大的，多功能的技术来理解一个重要的生物医学问题的结构生物学。这项研究将利用超快光学过程实验室的仪器-宾夕法尼亚大学的NIH研究资源。该实验室的建立是为了开发涉及红外光谱的新技术，用于生物大分子的研究，并为这类合作项目提供先进的仪器和专业知识。 公共卫生相关性：这是一个联合收割机二维红外光谱与氧化足迹/质谱和分子力学模拟相结合的建议，以回答有关淀粉样β蛋白原纤维的形成和结构的关键问题。

DESCRIPTION (provided by applicant): This is a proposal to combine two-dimensional infrared spectroscopy with oxidative footprinting / mass spectrometry and molecular mechanics simulation to answer key questions about the formation and structure of amyloid beta protein fibrils. There are two specific aims: 1. Correlate structure and morphology in amyloid fibrils. 2. Characterize the development of structure in oligomeric forms of A?. This project is an interdisciplinary collaboration between a physician-pharmacologist investigating the pathology of Alzheimer's disease, and a chemical physicist pioneering novel spectroscopic methods. We will be applying an emerging, powerful, and versatile technology for the first time to understanding the structural biology of an important biomedical problem. This research will make use of instrumentation in the Ultrafast Optical Processes Laboratory - an NIH Research Resource at the University of Pennsylvania. This laboratory was established to develop novel technologies involving infrared spectroscopy for the study of biological macromolecules, and to make advanced instrumentation and expertise available for collaborative projects of this type. PUBLIC HEALTH RELEVANCE: This is a proposal to combine two-dimensional infrared spectroscopy with oxidative footprinting / mass spectrometry and molecular mechanics simulation to answer key questions about the formation and structure of amyloid beta protein fibrils.