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计划正在支持旧自治领大学威廉和玛丽和珍妮弗·poutsma的约翰·C·普茨玛的合作研究。 John Poutsma组将采用基于质谱的实验来研究肽结构与其气相能量性能之间的相互作用。这项研究的重点是含有非蛋白质氨基酸（NPAA）的肽，这些肽在植物和真菌中自然发现，但不打算用于蛋白质合成。许多NPAA对人类和其他动物有毒，部分原因是与二十种普通蛋白质氨基酸（PAA）中的一个或多个结构相似。 NPAA可以在各种生物学途径中与PAAS竞争，包括将其分解为蛋白质和肽。研究已系统地替代NPAA的肽的行为将进一步了解肽结构及其在质谱仪中其行为之间的关系。最终，这种增强的理解可能会导致改善蛋白质组学实验的自动化肽测序算法。与这些实验合作，Jennifer Poutsma组将创建旨在支持和指导实验研究的计算模型。这两种研究计划将通过培训本科研究人员的培训来整合研究和教育组成部分。本提案中概述的大多数研究项目将由威廉和玛丽学院以及旧自治领大学的大学生进行。进行独立的研究不仅有助于教导这些学生的科学发现的乐趣，还可以教会如何处理和努力通过现实世界科学所面临的必然挑战。在这项研究中，将使用以下方面的肽的内在气相特性及其碎片来确定：1）使用：1）扩展的动力学方法，2）氢化型理论，3）基础型差异频谱和4次型速度降低了4）。这些研究的最终目标是进一步了解氨基酸结构与热化学特性之间的关系，以更好地了解分子内氢键对氨基酸和肽的气相化学的影响，并更好地了解低功能巨型tandem质谱实验中选择性碎片的机制。这些详细的知识可以整合到肽测序技术中，以更好地说明存在异常氨基酸的存在，并为选择性碎片。该奖项反映了NSF的法定任务，并且认为值得通过基金会的知识分子优点和更广泛的影响来通过评估来获得支持。