Structure determination by vibrational spectroscopy

描述(由申请人提供)：这是一项中试和可行性建议，旨在开发飞秒脉冲二维红外相关光谱(IR-COSY)作为确定淀粉样β蛋白结构的工具，这些淀粉样β蛋白形成平行的β片状纤维，很难用传统的结构生物学方法进行研究。该方法还将用于研究纤维形成过程中这种结构的演变。 阿尔茨海默病和其他几种疾病现在被认为涉及蛋白质的错误折叠和聚集，形成平行的β-折叠。更好地了解这种病理蛋白质结构是理解这些蛋白质最初错误折叠的关键，也是开发针对这些疾病的治疗干预措施的关键。

DESCRIPTION (provided by applicant): This is a pilot and feasibility proposal to develop femtosecond-pulse two-dimensional infrared correlation spectroscopy (IR-COSY) as a tool for structure determination in the amyloid beta proteins that form parallel beta sheet fibrils, and are difficult to study by the traditional methods of structural biology. The approach will also be applied to study the evolution of such structure during fibrillogenesis. Alzheimer's disease and several others are now recognized to involve the misfolding and aggregation of proteins as parallel beta sheets. A better understanding of this pathological protein structure is key to understanding why these proteins misfold in the first place, and to developing therapeutic interventions for these diseases.