Computational Studies on Nucleic Acid-Ion Interactions in Droplets and Bulk Solution
Interactions of macromolecules with ions in solution have a long history of study because of their ubiquitous nature. These interactions are essential for the stability and function of macromolecules such as nucleic acids. Nucleic acids are involved in many natural biochemical processes. For example, deoxyribonucleic acid (DNA) provides more than storage of genetic information. The guanine-rich structures, at the ends of the DNA, participate in regulating the gene expression in the living cell by forming guanine quadruplex (G-quadruplex) structures. These structures provide a possible drug target for the treatment of cancer. Nucleic acids are polyions under physiological pH of 7.4. Thus, DNA always associates with cations in the living cell. These cations are essential for maintaining DNA functions and structural stability. Experimental techniques showed that alkali metal cations are either diffused in the ionic atmosphere around the DNA duplex or are coordinated to the nucleotide bases. However, the experimental findings might not explain the nature of the interactions between metal cations and DNA at the atomistic level. To overcome some of the deficiencies with the experimental techniques, this thesis uses molecular modelling and simulation techniques to investigate the nucleic acid-ion interactions in droplets and bulk solution. The thesis first examines the charging of a poly(ethylene glycol) molecule because of its use as a typical test macromolecule in electrospray ionization mass spectrometry (ESI-MS), to obtain an understanding of the charging mechanism of the macroions in droplets. The analyses of the nucleic acid-solvent interactions and nucleic acid-ions interactions in droplets provide insights into the ESI-MS experiments on DNA complexes. In the bulk solution, free energy calculations examine the binding of individual sodium and potassium ions to guanine quadruplexes; the thesis reports the values of the Gibbs free energy and the binding constants of each cation. Additionally, the free energy calculations examine the effect of the guanine quadruplex flexibility on the binding of cations.
Molecular Modelling and Simulations, Charged Droplet Instability, Free Energy Calculations, DNA Duplex and Guanine Quadruplex
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