Fluorescence resonance energy transfer measurements of trapped mass-selected gas-phase ions of biological interest

活的生物系统是高度复杂的，它们的状态取决于许多难以理清的因素的相互作用，比如金属离子的存在，药物等结合伙伴的存在，甚至是永远存在的水分子。我们采取的方法是简化这些系统，并在一个高度受控的环境中研究它们，即气相。使用我们的质谱技术，可以完全分离出感兴趣的生物分子，如蛋白质（即可以完全消除环境），以研究其内在特性。然后，环境的一部分（水分子、金属离子、药物）可以以可控的方式添加回系统中，以便分别分析每种效应。我们分析蒸发离子，配合物和团簇使用传统的质谱技术和计算以及激光光谱技术，包括荧光技术，新适应于气相研究的组合。这项研究将为生物分子的结构、功能、稳定性和动力学提供新的基础信息，并将研究环境如何影响这些特性。我们将研究整个蛋白质和较短的氨基酸链，这些氨基酸链形成了蛋白质中较小的结构基序。这些研究将提供蛋白质折叠和错误折叠的理解，这可能导致许多毁灭性的疾病（如阿尔茨海默氏症和疯牛病）。它还将侧重于开发在质谱分析过程中保持关键相互作用的方法，例如药物与靶蛋白的结合。这在药物发现领域具有巨大的潜力。

Living biological systems are highly complex and their state depends on the interplay of numerous factors that can be difficult to untangle, such as the presence of metal ions, binding partners such as drugs, and even the ever present water molecules. The approach we take is to simplify these systems and study them in a highly controlled environment, the gas phase.  Using our mass spectrometry techniques, a biological molecule of interest such as a protein can be completely isolated (i.e., the environment can be eliminated entirely) to study its intrinsic properties.  Then pieces of the environment (water molecules, metal ions, drugs) can be added back into the system in a controlled manner in order to analyze each effect separately. We analyze the vaporized ions, complexes and clusters using a combination of traditional mass spectrometry techniques and computations as well as laser spectroscopic techniques including fluorescence techniques, newly adapted for gas-phase studies. The research will provide new fundamental information regarding biomolecular structure, function, stability and dynamics and will investigate how the environment affects these properties. We will examine both whole proteins and shorter chains of amino acids that form the smaller structural motifs present in proteins. These studies will provide understanding of protein folding and misfolding, which can cause many devastating diseases (e.g. Alzheimer's and mad cow disease). It will also focus on the development of methods to maintain key interactions during mass spectrometry analysis, such as the binding of drugs to target proteins. This has great potential in the field of drug discovery.