Collaborative Research: Intrinsic Gas-Phase Acid-Base Properties and Structures of Non-Protein Amino Acids and Non-Protein Amino Acid-Containing Peptides

通过这一奖项，化学结构、动力学和机制-B项目支持威廉与玛丽学院的约翰·C·普特斯马和老道明大学的珍妮弗·普特斯马的合作研究。John Poutsma的团队将使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相互作用。这项研究的重点是含有非蛋白生成氨基酸(NPAA)的多肽，NPAA天然存在于植物和真菌中，但不用于蛋白质合成。许多NPAA对人类和其他动物是有毒的，部分原因是结构上与20种常见的蛋白原性氨基酸(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，将有助于我们进一步了解多肽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。在与这些实验的合作中，詹妮弗·普特斯玛小组将创建旨在支持和指导实验研究的计算模型。这两个研究项目都将通过培训本科生研究人员来整合研究和教育部分。本提案中概述的大多数研究项目将由威廉与玛丽学院和老多米尼恩大学的本科生进行。进行独立研究不仅有助于教这些学生喜悦科学发现，而且还帮助他们处理和克服现实世界科学中不可避免的挑战。在这项研究中，多肽及其碎片的本征气相性质将通过以下方法确定：1)扩展动力学方法，2)氢-氢交换，3)红外多光子解离光谱和4)密度泛函理论计算。这些研究的最终目的是进一步了解氨基酸结构和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，以及更好地了解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技术中，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-B program is supporting the collaborative research of John C. Poutsma at the College of William and Mary and Jennifer Poutsma at Old Dominion University. The group of John Poutsma will employ mass spectrometry-based experiments to study the interplay between the structure of peptides and their gas-phase energetic properties. This study focuses on peptides containing non-proteinogenic amino acids (NPAA), which are found naturally in plants and fungi, but are not intended for 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 proteinogenic 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 will further our understanding of the relationship between peptide structure and its behavior in the mass spectrometer. Ultimately, this enhanced understanding may lead to improved automated peptide sequencing algorithms for proteomics experiments. In collaboration with these experiments, the group ofa Jennifer Poutsma will create computational models intended to support and guide the experimental studies. Both research programs will integrate research and educational components through the training of undergraduate researchers. A majority of the research projects outlined in this proposal will be performed by undergraduates at the College of William and Mary and at Old Dominion University. Performing independent research helps to teach these students not only the joy of scientific discovery but also how to handle and work through the inevitable challenges that accompany real-world science.In this research, intrinsic gas-phase properties of peptides and their fragments will be determined using: 1) the extended kinetic method, 2) hydrogen-deuterium exchange, 3) infrared multiphoton dissociation spectroscopy and 4) density functional theory calculations. The ultimate goals of these studies are to further understanding of 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 better understand the mechanisms for selective fragmentations in low-energy tandem mass spectrometry experiments. This detailed knowledge can be integrated into peptide sequencing technology to 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.