Document Type



Doctor of Philosophy (PhD)



First Advisor's Name

Francisco Fernandez Lima

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Jaroslava Miksovska

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Hebin Li

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Bruce McCord

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Yi Xiao

Fifth Advisor's Committee Title

Committee member


Ion mobility spectrometry, mass spectrometry, molecular modeling, analytical chemistry, infrared multiphon dissociation, FT-ICR MS, TIMS-MS

Date of Defense



The following thesis comprises the use of novel gas-phase spectroscopic and spectrometric techniques complemented with molecular dynamics for the structural characterization of biomolecules: from small model systems to large proteins. In particular, complementary linear and non-linear ion mobility, mass spectrometry and action spectroscopy has been applied to the separation and characterization of native and kinetic intermediate states of biomolecular ions. This suite of tools, comprising ion mobility in tandem with non-ergodic fragmentation and action spectroscopy, provided unique information on the conformational space, folding and binding dynamics of single stranded DNA, peptides, peptide-cofactor and protein systems. Theoretical modeling provided candidate structures filtered by measurements of molecular ion-neutral collision cross section, fragmentation patterns and infrared spectroscopy data. In addition, this work covers the development of higher power analytical separations with increased peak capacity, reduced chemical noise and reduced analysis time for the characterization of complex biological mixtures (e.g., cell digests).



Previously Published In

Chapter 2: Benigni, P, Porter, J, Ridgeway, ME, Park, MA, Fernandez-Lima, F. Increasing Analytical Separation and Duty Cycle with Nonlinear Analytical Mobility Scan Functions in TIMS-FT-ICR MS. Anal Chem. 2018; 90 (4): 2446-2450

Chapter 3: Porter, JE, Chapagain, P, Fernandez‐Lima, F. Single‐stranded DNA structural diversity: TAGGGT from monomers to dimers to tetramer formation. Rapid Commun Mass Spectrom. 2019; 33( S2): 60– 65.



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