Table 4.
Contributions of Key Nucleobases and Water Molecules in Stabilizing the Intermediate and Transition States from In-Line Monoanionic and A38(+) Mediated Mechanismsa
| in-line O1P |
in-line O2P |
A38(+)+O1Pb |
A38(+)+O2Pb |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| range (Å)c | TSPT1 | INT2 | TSCl | TSPT1 | INT2 | TSCl | TSPT1 | INT2 | TSCl | TSPT1 | INT2 | TSCl |
| Ribozyme strand | ||||||||||||
| G8 | 4.9 | -2.9 | 2.5 | 1.2 | -0.8 | 5.3 | 17.0 | -1.7 | 1.7 | -9.3 | -4.9 | 7.8 |
| A9 | 2.1 | 0.1 | 6.8 | 1.0 | -1.1 | 3.4 | 4.7 | 5.1 | 4.6 | -1.0 | -1.7 | -0.8 |
| A10 | -2.8 | 0.7 | 2.0 | 0.0 | 0.2 | 0.5 | -2.3 | -1.5 | -0.8 | -0.3 | 0.0 | 0.4 |
| C25 | 0.9 | -1.2 | -1.5 | 0.2 | 0.6 | 0.0 | -1.9 | -2.4 | -2.9 | -2.8 | -1.1 | -1.1 |
| A38 | -0.2 | 0.1 | 0.3 | -2.2 | 1.0 | 2.0 | -0.3 | 0.2 | -16.8 | -5.5 | -18.3 | -41.5 |
| Substrate strand | ||||||||||||
| A-1 | -0.7 | -1.0 | 0.2 | -2.1 | -0.3 | -0.1 | -1.5 | 0.5 | 0.5 | 0.2 | 0.9 | 1.0 |
| G+1 | -5.0 | 2.0 | 3.2 | -1.1 | 0.5 | 2.8 | -1.5 | 1.6 | 0.3 | 7.7 | 4.6 | 8.4 |
| U+2 | 0.1 | -1.4 | -3.0 | 2.1 | 0.6 | -1.6 | 1.2 | 1.3 | -0.1 | 1.2 | 1.8 | 1.6 |
| C+3 | 5.6 | -2.9 | -5.7 | 3.6 | 5.2 | 3.9 | -0.3 | -1.5 | -2.3 | -1.2 | 1.3 | 1.2 |
| Water molecules | ||||||||||||
| water (1-3) | 0.4 | 0.2 | 0.5 | 0.5 | -0.3 | -4.3 | 0.5 | 0.4 | 0.5 | -1.8 | -1.1 | 1.5 |
| (3-5) | 8.9 | 2.3 | -18.9 | -0.2 | -8.1 | -21.6 | -14.6 | -12.6 | -1.1 | 14.9 | 16.2 | 13.3 |
a
Energy values are computed as ΔEX = ⟨EX⟩ - ⟨EReact⟩, where X denotes intermediate and transition states, EX is the interaction energy in kcal/mol of the specified base or water molecules with the scissile phosphate group, and react is reactant state, in the QM/MM molecular dynamics simulations.
b
In the A38(+) mediated mechanism, A38 base, which is protonated at the N1 site, is excluded from the QM subsystem for the consistent comparison with other mechanisms and represented by point charges.
c
The distance range in Å of the water molecules from the center of quantum region.