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

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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.