Conformational Dynamics of Biomolecules by Trapped Ion Mobility Spectrometry Dynamics

Authors

Juan Camilo Molano-Arévalo, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Chemistry

First Advisor's Name

Francisco Fernandez-Lima

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Alexander Mebel

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Fenfei Leng

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Jessica Liberles

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Jeff Joens

Fifth Advisor's Committee Title

Committee Member

Keywords

Ion Mobility Spectrometry, Mass Spectrometry, Structural Biology, Analytical Chemistry

Date of Defense

4-16-2018

Abstract

One of the main goals in structural biology is to understand the folding mechanisms and three-dimensional structure of biomolecules. Many biomolecular systems adopt multiple structures as a function of their microenvironment, which makes them difficult to be characterized by traditional structural biology tools (e.g., NMR, X-ray crystallography). As an alternative, complementary tools that can capture and sample multiple conformations needed to be developed. In the present work, we pioneered the application of a new variant of ion mobility spectrometry, trapped ion mobility spectrometry (TIMS), which provides high mobility resolving power and the possibility to study kinetically trapped intermediates as a function of the starting solution (e.g., pH and organic content) and gas-phase conditions (e.g., collisional activation, molecular dopants, hydrogen/deuterium back-exchange). When coupled to mass spectrometry (TIMS-MS), action spectroscopy (IRMPD), molecular dynamics and biochemical approaches (e.g., fluorescence lifetime spectroscopy), a comprehensive description of the biomolecules dynamics and tridimensional structural can be obtained. These new set of tools were applied for the first time to the study of Flavin Adenine Dinucleotide (FAD), Nicotineamide Adenine Dinucleotide (NAD), globular protein cytochrome c (cyt c), the 3₁ knot YibK protein, 5₂ knot ubiquitin C terminal hydrolase (UCH) protein, and the 6₁ knot halo acid dehydrogenase (DehI) protein.

Identifier

FIDC006557

Recommended Citation

Molano-Arévalo, Juan Camilo, "Conformational Dynamics of Biomolecules by Trapped Ion Mobility Spectrometry Dynamics" (2018). FIU Electronic Theses and Dissertations. 3647.
https://digitalcommons.fiu.edu/etd/3647