INVESTIGATING THE EFFECTS OF IONIC LIQUIDS ON DNA GQUADRUPLEX AND PROTEIN STRUCTURE USING MOLECULAR DYNAMICS SIMULATIONS
M.S. Pharmaceutical Sciences
Chemistry and Biochemistry
College of Science & Mathematics
Chun Wu, Ph.D.
Committee Member 1
Subash Jonnalagadda, Ph.D.
Committee Member 2
Gregory A. Caputo, Ph.D.
Committee Member 3
Thomas M. Keck, PhD.
Azurin, DNA, G-Quadruplexes, Ionic Liquids, Molecular Dynamics Simulations, TMPyP
Biopharmaceutics; Nucleic acids
Nucleic acids and proteins have huge implications in biomedicine and bioengineering, however their storage instability limits their applicability and current storage protocols are expensive and globally-inaccessible. Finding an alternative biocompatible media to store nucleic acids and proteins would reduce costs and increase their applicability. Ionic liquids (ILs) are molten salt compounds that have been shown to modulate the stability and activity of nucleic acids and proteins. In this thesis, molecular modeling studies of DNA/RNA and protein structure in ILs will be discussed (Chapter 1) and this method will be used to study the IL effects on the structure on the Pu22 c-MYC DNA G-quadruplex (Chapter 2) and the azurin protein (Chapter 3). ILs have been observed to stabilize/destabilize DNA G-quadruplexes linked to cancer oncogene expression, however the structural effects of imidazolium-based ILs on G-quadruplexes remain unknown. Bioengineering of azurin is attractive for soil bioremediation, thus understanding the structural changes induced by TMG amino acid-based ILs will mediate future IL design for enhancing azurin's activity. In Chapter 2, molecular dynamics (MD) simulations will elucidate the stabilizing mechanism of four imidazolium-based ILs of increasing hydrophobicity to Pu22, using the G-quadruplex stabilizer TMPyP4 as a molecular probe. In Chapter 3, conventional and replica-exchange MD simulations will provide insight into the enthalpic and entropic change induced by two TMG-AA based ILs on the folded and unfolded azurin conformations.
Paradis, Nicholas J., "INVESTIGATING THE EFFECTS OF IONIC LIQUIDS ON DNA GQUADRUPLEX AND PROTEIN STRUCTURE USING MOLECULAR DYNAMICS SIMULATIONS" (2022). Theses and Dissertations. 3074.