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

说明(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、快速和用户友好的工具。这项技术也是最敏感的技术之一。随着成像分辨率的衍射极限被突破，荧光单分子的成像成为可能。事实上，单分子成像开启了细胞电影的可能性，因此也就开启了对细胞过程的分子水平的理解。然而，目前对色氨酸的光谱解释水平远未达到分子水平。这是因为色氨酸荧光数据被几个叠加因素复杂化，包括溶剂松弛、多构象和非辐射衰变。这项研究通过分子动力学模拟和光谱方法解决了色氨酸荧光数据解释的低分辨率问题。这项研究的目标是创建一个荧光光谱参数矩阵，这些参数将构成特定色氨酸环境和蛋白质构象的“指纹”。随着光谱解释的改进，这项工作将影响人类的健康和福祉，这两个指令都是NIH的指令，因为对蛋白质功能的了解，因此药物与疾病相关蛋白质的相互作用将得到极大改善，缩短药物开发时间。

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.