Date of Award
12-16-2020
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Gregory M. K Poon
Second Advisor
W. David Wilson
Third Advisor
Jenny J. Yang
Fourth Advisor
Donald Hamelberg
Abstract
Target recognition by DNA-binding ligands, such as drugs, occurs in an aqueous environment, in which water (near unit mole fraction, ~55 M) dominates every solute. A quantitative account of how water molecules are disposed in DNA/ligand binding is indispensable for understanding the driving forces that confer high-affinity and selectivity. We are investigating the DNA sequence selectivity of a model DNA minor groove-binding heterocyclic diamidine, DB1976, which shows therapeutic activity in acute myeloid leukemia, systemic fibroses, and obesity-related liver disorders in vivo. The DNA minor groove is richly populated with water molecules. Studies based on explicit-solvent MD simulation have shown distinct DNA dynamics upon drug-DNA complexes. We have cooperated the role of hydration and conformational dynamics in contributing to drug selectivity. Moving forward, our goal is to evaluate the structure-hydration relationships of designed diamidines to site-specific and nonspecific DNA as part of their biophysical characterization as potential therapeutic agents.
DOI
https://doi.org/10.57709/20511045
Recommended Citation
Ha, Van, "Investigating the Role of Hydration and DNA Dynamic Alterations in DNA Recognition by A Heterocyclic Diamidine." Thesis, Georgia State University, 2020.
doi: https://doi.org/10.57709/20511045
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