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

合作研究：非蛋白质氨基酸和非蛋白质氨基酸肽的内在气相酸碱性质和结构

• 批准号: 2154537
• 负责人: John Poutsma
• 金额: $ 19.93万
• 依托单位: College of William and Mary
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154537&HistoricalAwards=false
• 关键词: Collaborative; Research; Intrinsic; Gas; Phase

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.

有了这个奖项，化学结构，动力学和机制-B计划是支持合作研究的约翰C。普茨玛在威廉和玛丽学院和詹妮弗普茨玛在旧自治领大学。John Poutsma小组将采用基于质谱的实验来研究肽的结构与其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质氨基酸（NPAA）的肽，这些氨基酸天然存在于植物和真菌中，但不用于蛋白质合成。许多NPAAs对人类和其他动物有毒，部分原因是与二十种常见蛋白原氨基酸（PAA）中的一种或多种结构相似。NPAA可以在多种生物学途径中与PAA竞争，包括错误掺入蛋白质和肽中。研究NPAAs系统取代肽的行为将进一步加深我们对肽结构与其在质谱仪中行为之间关系的理解。最终，这种增强的理解可能会导致蛋白质组学实验的自动化肽测序算法的改进。与这些实验合作，Jennifer Poutsma小组将创建旨在支持和指导实验研究的计算模型。这两个研究计划将通过本科研究人员的培训整合研究和教育成分。本提案中概述的大部分研究项目将由威廉和玛丽学院以及旧自治领大学的本科生进行。进行独立研究有助于教这些学生不仅科学发现的乐趣，而且还如何处理和工作，通过伴随着现实世界的科学不可避免的挑战。在这项研究中，肽及其片段的固有气相特性将使用确定：1）扩展动力学方法，2）氢-氘交换，3）红外多光子解离光谱和4）密度泛函理论计算。这些研究的最终目标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肽的气相化学的影响，并更好地了解低能串联质谱实验中选择性碎片化的机制。这些详细的知识可以被整合到肽测序技术中，以更好地解释不寻常氨基酸的存在，以及选择性片段化。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。