Journal:JBSD:5

Influence of divalent magnesium ion on DNA: molecular dynamics simulation studies

Sanchita Mukherjee and Dhananjay Bhattacharyya^[1]

Molecular Tour
The polyelectrolyte behavior is one of the most important physicochemical properties of DNA. This behavior is dependent on the interaction of counterions with DNA, which plays a crucial role in stabilizing the double helix. Two B-DNA crystal structures, namely PDB ID 1d49, d(CGATTAATCG) containing one crystallographic hexahydrated magnesium ion and PDB ID 436d, d(CGCGAATTCGCG) with five crystallographic magnesium ions, among which one is coordinated to a phosphate oxygen and rest of them hexahydrated, were obtained from PDB. These systems were then neutralized with required number of sodium ions solvated with water molecules. Molecular dynamics simulations are carried out for each of them for 100 ns to understand dynamics of DNA and especially the magnesium ions around the DNA. In 384d the six water oxygen atoms (in red) near the Mg²⁺ ions (colored in green) .

In order to get the positions of the magnesium ion with respect to DNA throughout the simulation, an average structure of DNA has been calculated first and then the positions of the magnesium ions were mapped on the average structure following periodic boundary condition with appropriate box dimension at each time step. To get the flavor of most occupied positions of Mg²⁺ in the entire box we divided the box into (2Å)³ grids and calculated the frequency of the ion in each grid throughout the simulation time. The grids with high frequencies are taken to predict the most likely positions of Mg²⁺. This gives an opportunity to visualize the positions and restrictions of the ion movements with respect to the DNA. The highest frequency for the is seen in the minor groove with grid frequency equivalent to that of 3 ns, but this corresponds to the initial crystal structure position of the ion. When it moves out of the minor groove high frequency is seen in major groove also (~1 ns) with more grids in number in the vicinity of major groove. The coordinated Mg²⁺ site corresponds to the highest frequency region around the . Both major and minor grooves of the dodecamer contain high frequency (equivalent to about 800 ps) points corresponding to the presence of Mg²⁺. It is worth noting that high frequency points are also larger in number for major groove due to availability of more space in the major groove. This implies diminished movement of bulky magnesium in narrow minor groove and more flexible movement in wider major groove and could reason straightaway the preference of major groove.

Occupancy is defined as the simulation time during which a counterion was within a specific cutoff distance from a DNA atom in case of hydrated ions. The occupancy values were calculated for all the surface atoms of DNA to detect the highly preferred sites for magnesium. We found phosphate oxygen of the 4th residue in decamer to have the maximum occupancy (corresponding to 2 ns). We could select 28 such atoms having significant occupancy values in case of the . It indicates that the phosphate oxygen atoms come in close contact maximally while some nitrogen (N7) and base oxygen also have significant occupancy. Few non-polar hydrogen atoms are also seen to make water mediated contacts with the hydrated Mg²⁺ ions. Similar high occupancy in the is seen for O1P of the 9th residue. Quit a few N7 atoms, O4, O3’ and O2 are also found near Mg²⁺ for significant durations. Guanine 2-amino group also was found close to the hexahydrates.