Date of Graduation


Document Type


Degree Type



Eberly College of Arts and Sciences



Committee Chair

Stephen J. Valentine

Committee Co-Chair

Blake Mertz

Committee Member

Brian Popp

Committee Member

Fabien Goulay

Committee Member

Mark McLaughlin


Mass spectrometry (MS) based-techniques and molecular dynamics (MD) simulations have been used to characterize protein/peptide structure as well as their interactions with lipid vesicles and detergents. Chapter 1 introduces an introduction to the concepts and tools that were used in this work. In Chapter 2, the dominant gas-phase conformer of [M+3H]3+ ions of the model peptide Acetyl-PSSSSKSSSSKSSSSKSSSSK are examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. This section furthers the development of a protein structural prediction tool by providing information about gas-phase ion conformers of two model peptides having different solution conformational states. In Chapter 3, interactions between the first 17 amino acid residues (Nt17 peptide) of the Huntingtin protein (htt) with lipid vesicles comprised of two subclasses of phospholipids are examined using electrospray ionization - mass spectrometry (ESI-MS) and MD simulations. Notably, the aggregation of Htt results in Huntington’s disease (HD). Chapter 4 presents a MD simulations study of proteorhodopsin (PR) oligomers in different membrane environments. Proteorhodopsins are transmembrane proteins and members of the microbial rhodopsin family which act as a proton pump in the bioenergetics processes in bacteria. Finally, Chapter 5 discusses future directions for utilizing experimental and computational methods to obtain information about protein/peptide structure. Overall, the combination of MS-based techniques and MD simulations is shown to provide unique and enhanced structural information for intractable protein/peptide species.

Embargo Reason

Publication Pending

Available for download on Saturday, November 13, 2021