RUI: Collaborative Research: Intrinsic Gas-phase Properties of Peptides: Thermochemistry, Fragmentation Mechanisms, H/D exchange and IRMPD Spectroscopy.

通过这一奖项，化学结构、动力学和机制计划支持威廉与玛丽学院的John C.Poutsma教授和Old Dominion大学的Jennifer Poutsma教授的合作研究。John Poutsma教授利用基于质谱学的实验来研究多肽的结构和它们的气相能量特性之间的微妙相互作用。他研究含有非蛋白质氨基酸(NPAA)的多肽，NPAA天然存在于植物和真菌中，但不用于天然蛋白质合成。许多NPAA对人类和其他动物有毒，部分原因是结构上与20种常见蛋白质氨基酸(PAA)中的一种或多种相似。NPAA可以通过多种生物途径与PAAS竞争，包括被误结合到蛋白质和多肽中。研究NPAA被系统取代的多肽的行为有助于了解多肽的结构与其在质谱计中的行为之间的关系。最终，这种增强的理解可能会导致蛋白质组学实验中改进的自动化多肽测序算法。Jennifer Poutsma教授进行密度泛函理论计算，以预测支持和指导实验研究的结构和能量学。这两个研究项目都通过本科生研究人员的培训将研究和教育部分整合在一起。这项研究是由威廉、玛丽和老道明大学的本科生进行的。在这项研究中，多肽及其碎片的本征气相性质是通过1)扩展动力学方法、2)氢氚交换、3)红外多光子解离光谱、4)多肽裂解研究和5)密度泛函计算来确定的。这些研究的最终目的是建立氨基酸结构与热化学性质之间的关系，更好地了解分子内氢键对氨基酸和多肽的气相化学的影响，并解释低能串联质谱学实验中选择性裂解的机制。这种详细的知识可以整合到多肽测序方法中，这样它们就可以更好地解释异常氨基酸的存在和选择性碎片。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemical Structure, Dynamics and Mechanisms program is supporting the collaborative research of Professor John C. Poutsma at the College of William and Mary and Professor Jennifer Poutsma at Old Dominion University. Professor John Poutsma employs mass spectrometry-based experiments to study the subtle interplay between the structure of peptides and their gas-phase energetic properties. He studies peptides containing non-protein amino acids (NPAA), which are found naturally in plants and fungi, but are not used in natural protein synthesis. Many NPAAs are toxic to humans and other animals in part due to structural similarity to one or more of the twenty common protein amino acids (PAA). NPAAs can compete with PAAs in a variety of biological pathways including being mis-incorporated into proteins and peptides. Studying the behavior of peptides into which NPAAs have been systematically substituted helps to understand the relationship between a peptide's structure and its behavior in the mass spectrometer. Ultimately this enhanced understanding may lead to improved automated peptide sequencing algorithms for proteomics experiments. Professor Jennifer Poutsma performs density functional theory calculations to predict structure and energetics that support and guide the experimental studies. Both research programs integrate research and educational components through the training of undergraduate researchers. This research is carried out by undergraduates at William and Mary and Old Dominion University. Performing independent research helps to teach these students not only the joy of discovery but also how to handle and work through the inevitable failures that accompany real-world science.In this research, intrinsic gas-phase properties of peptides and their fragments are determined using 1) the extended kinetic method, 2) hydrogen deuterium exchange, 3) infrared multiphoton dissociation spectroscopy, 4) peptide fragmentation studies and 5) density functional computations. The ultimate goals of these studies are to establish the relationship between amino acid structure and thermochemical properties, to better understand the effects of intramolecular hydrogen bonding on the gas-phase chemistry of amino acids and peptides, and to explain the mechanisms for selective fragmentations in low-energy tandem mass spectrometry experiments. This detailed knowledge may be integrated into peptide sequencing methods so that they can better account for the presence of unusual amino acids, and for selective fragmentations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.