A Molecular Dynamics View of Counterionic Effects on Structural Dynamics

Molecular dynamics simulations are a powerful tool for elucidating stationary and dynamic features of chemical systems with atomistic resolution. This dissertation studies the effects of counterions on structural dynamics utilizing molecular dynamics. In particular, I investigate the following systems: (1) the distribution of counterions surrounding deoxyribonucleic acid (DNA) using an empirically charge screened forcefield, (2) the structural dynamics of DNA with minor-groove binder Hoechst 33258, (3) the dynamics of the electrolyte solutions with fluoroethylene additive, and (4) the aggregation of phosphate anions in the presence of sodium counterions.

Current experimental and simulated sodium counterion distribution data for DNA do not align. To address this difference, an empirical charge screening force field is applied to the sodium counterions around a double-stranded DNA oligonucleotide with sequence, d(CGCGAATTCGCG)₂. When the sodium counterions are systematically scaled, the radial distribution begins to show a first solvation shell minimum at approximately 3.7 Å, which has typically not been captured in molecular dynamics simulations with conventional charge methods. The presence of the first solvation shell is driven by the formation of three unique binding sites in the minor groove at the C3-A4, A6-T7, and T9-G10 base pair steps. Charge scaling in DNA leads to a more accurate counterion atmosphere.

Understanding the interactions of ligands with DNA is important in DNA-based nanotechnologies and drug design. Structural changes in the DNA can be tracked using molecular dynamics and it is shown that Hoechst 33258 strongly disturbs the stability of the terminal C:G base pairs. The strong stabilization effect of the Hoechst 33258 on DNA duplex makes this observation quite striking, and simulations demonstrate an important role of hydration water and counterions in maintaining the separation of terminal base pairs. The hydrogen bonds between Hoechst 33258 and the thymine carbonyls are crucial in stabilizing H-DNA, but the ligand is only able to form two hydrogen bonds at most with the DNA, unlike the traditional interpretation of four hydrogen bonds.

Additives have been shown to increase the lifetime of rechargeable batteries, however, little is known what causes the change. Fluoroethylene carbonate is studied in this thesis by adding 5% by volume to a 1:1:1 mass ratio mixture of dimethyl carbonate, diethyl carbonate, and ethylene carbonate and simulating the mixture with fluoroethylene carbonate, the mixture without fluoroethylene carbonate, and a pure fluoroethylene carbonate solution. Fluoroethylene carbonate is shown to experience weaker interactions with dimethyl carbonate, diethyl carbonate, and ethylene carbonate than when interacting with itself. The addition of fluoroethylene carbonate also alters the structural orientation of ethylene carbonate in the mixture, which could cause the change in the overall solution behavior.

Phosphate plays a major role in energy storage and transfer in biochemical processes and is commonly found partially deprotonated as a dihydrogen phosphate anion. Dihydrogen phosphate anions are known to form interanionic hydrogen bonds, which can be characterized by a maximum bond length of 2.5 Å and a minimum bond angle of 120°. Oligomers of dihydrogen phosphates are formed and are revealed to be concentration dependent. Counterion-pairing of the oligomers is also concentration dependent but also has dependency on the oligomer size. To determine the exact role of counterions in oligomer formation, further analysis is needed.