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

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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.