Extended Data Figure 5: Molecular dynamics simulation analysis of 8-oxo-dGTP(anti) and dGTP(anti) opposite Cy.
From: Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide
a, The 8-oxo-dGTP(anti) opposite Cy at 80 ns superimposed upon the initial structure. A multicolour code based on atom type is used for the final molecular dynamics structure, whereas the reference initial structure is shown in light grey. The catalytic (Mgc), nucleotide (Mgn), and ground (Mgg) magnesium metal ions are shown in green, and average distances over the course of the simulation are indicated for Pα-O3′ and Mgc-O3′. b, Distance distributions between hydrogen atoms in the water shell and O8 in the 8-oxo-dGTP(anti):Cy simulation. A snapshot of the 8-oxo-dGTP, Mgg, and water shell (W(g1–g5)) is plotted at top. Black and red dotted lines indicate Mgg coordination and a hydrogen-bonding interaction between a water molecule and O8, respectively. Four of the five water molecules in the water shell (W(g1–g4)) contribute to hydrogen-bonding interactions with O8. Blue and orange lines indicate distances between hydrogen atoms in each water molecule and O8. The red line in the bottom plot indicates the minimum distance between hydrogen atoms in the water shell and O8. c, The dGTP(anti) opposite Cy at 80 ns superimposed upon the initial structure (grey). Distances and ion labelling are as for a. d, Root mean squared deviation of the evolving molecular dynamics structure for the entire polymerase/DNA complex (top) and for the active site only (bottom), with respect to the crystal structure.
