Figure 2.
(A) When the H4 tail (green surface) is unacetylated, it is collapsed on the DNA minor and major grooves, and interacts with the cis-B[a]P-dG lesion. (B) When acetylated, the H4 tail is released from the DNA surface, as reflected in the inserted histogram which gives the contact surface area (CSA) between the H4 tail and the DNA surface. Also in (B), the partner base C to the cis-B[a]P-dG lesion is flipped out and can be captured by the nearby H3 tail, which is rearranged to form a pocket (yellow surface) for the C base. The pocket and its volume were computed using the POCASA web server [64]. The pocket is surrounded by amino acid residues Pro16, Arg17, Lys18, Ser28, Ala29, Pro30, Ala31, Pro38, His39, and Tyr41 (purple surface). The amino acids comprising the pocket were computed with the CASTp web server [65–67]. These residues are rendered in purple surface in both (A) and (B) to highlight the rearrangement of the H3 tail upon H4 tail acetylation. (A) and (B) show the same region of interest as in Figure 1B. The N-terminus of each tail is shown as a black sphere. The color code is the same as in Figure 1. See also Movies S1 and S2. (C) Transition of the C opposite the cis-B[a]P-dG lesion into the varying-sized pocket of the H3 tail when the H4 tail is acetylated. Only the window highlighted in the grey box in (B) is shown. (i) A snapshot at ~1.2 µs, where the partner C is on the major groove side and the pocket has formed. (ii) an intermediate snapshot between 1.2 µs and 1.3 µs, in which the partner C is flipped out but is not yet captured by the pocket. (iii) A snapshot at ~1.3 µs, in which the partner C has been captured by the pocket in the H3 tail. The dihedral angles (defined in (D)) for (i), (ii), and (iii) are respectively, 76 °, 140 °, and 157 °. The pocket volumes are respectively, 61, 39, and 59 Å2. See also Movie S3. (D) The flipping dihedral angle a-b-c-d is defined as the center of mass of 4 groups, a, b, c, and d; a is the base A that is the 5’- neighbor to the partner C; b is the sugar of the 5’- neighbor base A to the partner C; c is the sugar of the partner C; and d is the partner base C. (E) Time dependence of the flipping dihedral angle of the partner base C for the lesion-containing NCP with the H4 tail in unacetylated state (blue line) and in acetylated state (red line). (F) Time dependence of van der Waals interactions between the partner C base and the H3 tail residues that are components of the pocket that can capture the partner base C when the H4 tail is acetylated.