Energy analysis of chemistry for correct insertion by DNA polymerase β

Lin et al. 10.1073/pnas.0606006103.

Supporting Information

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Supporting Figure 3
Supporting Figure 4
Supporting Figure 5
Supporting Table 1
Supporting Table 2
Supporting Text




Supporting Figure 3

Fig. 3. Schematic representation of the QM/MM partition in the reactive state structure. (a) The system selected for the QM/MM calculation. QM atoms are in ball-and-stick format, dsDNA (stick), complete DNA polymerase b (cartoon and lines, hydrogen atoms not shown), counter ions (Na⁺ and Cl^-, spheres), and selected waters (up to 15 Å from QM atoms) are also included. Only MM atoms within 10 Å of the QM atoms are allowed to move during the optimization. (b) Optimized active-site initial state structure. Key distances are listed with reference to the experimental values (in parentheses) in the gapped DNA-2'-deoxy-uridine-5'-(a,b)-imido triphosphate-pol b complex.

Supporting Figure 4

Fig. 4. Schematic minimum energy path along the potential surface (arbitrary reaction coordinate). Reaction state (RS), local minimum state after the proton transfer to Asp-256 (LM), TS, and product state (PS) are connected with a 0.1-Å step along O3'-P1A and P1A-O3A distances. Both open and filled circles are calculated points.

Supporting Figure 5

Fig. 5. Schematic of the TS structure of the active site. Residues with significant contribution to the electrostatic stabilization of TS are also included.

Table 1. Residue TS stabilizations (kcal/mol) based on electrostatic calculations and mutagenesis data

Domain/subdomain nomenclature is according to Beard et al. (21): Lyase,domain (L) and the DNA binding (D), DNA synthesis (C), and dNTP selection (N) subdomains of the polymerase domain. * denotes that the residue is preserved in at least two X-family members (pol b, pol l, pol m, TdT).

^†Energy relative to the energy of ground state (GS).

^‡Energy relative to the proton-transferred local minimum state (LM).

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Table 2. The atomic charges of the dTTP molecule generated by using the restrained electrostatic potential (RESP) method