Edge-on/face-on: Trp tripeptides model residue interactions in proteins

描述（申请人提供）：色氨酸的荧光光谱是研究疾病相关蛋白质结构和功能的一种方便、快速和易用的工具。这项技术也是最敏感的技术之一。由于突破了图像分辨率的衍射极限，对荧光单分子的成像成为可能。事实上，单分子成像开启了拍摄细胞电影的可能性，从而在分子水平上理解细胞过程。然而，目前色氨酸的光谱解释水平离分子水平还很远。这是因为色氨酸荧光数据是复杂的几个重叠的因素，包括溶剂松弛，多重构象，和非辐射衰变。提出的研究通过分子动力学模拟和光谱方法解决色氨酸荧光数据解释的低分辨率问题。该研究的目标是创建一个荧光光谱参数矩阵，该矩阵将构成蛋白质中特定色氨酸环境和构象的“指纹”。随着光谱解释的改进，这项工作将对人类健康和福祉产生影响，这是NIH的两个指令，因为对蛋白质功能的理解，因此，药物与疾病相关蛋白质的相互作用，将大大改善，减少药物开发的时间。

DESCRIPTION (provided by applicant): Fluorescence spectroscopy of the amino acid, tryptophan, is a convenient, rapid and user- friendly tool for studying the structure and function of disease-related proteins. The technique is also among the most sensitive. As the diffraction limit to image resolution is breached, imaging of fluorescent single molecules becomes possible. Indeed, single molecule imaging opens the possibility of a movie of the cell, and therefore molecular level understanding of cellular processes. The current level of spectral interpretation for tryptophan, however, is far from the molecular level. This is because tryptophan fluorescence data is complicated by several overlying factors, which include solvent relaxation, multiple conformers, and nonradiative decay. The proposed research addresses the low resolution of data interpretation for tryptophan fluorescence through both molecular dynamics simulation and spectroscopic methods. The goal of the research is to create a matrix of fluorescence spectral parameters that will constitute a 'fingerprint' for specific tryptophan environments and conformations within proteins. With an improvement in spectral interpretation, this work will impact on human health and well-being, both directives of the NIH, because understanding of protein function, and therefore, drug interaction with disease-related proteins, will be greatly improved, cutting the time to drug development.