FIGURE 1.

Two-dimensional free energy surfaces for in-line monoanionic mechanisms for the (A) uncatalytic model reaction in solution, the catalytic (B) O_1P and (C) O_2P pathways in the hairpin ribozyme (HPR), and the (D) G8-assisted dianionic general base catalytic mechanism of the HPR, in which the 2′-proton is transferred to the N₁ of a deprotonated G8. For both mechanisms, ζ₁ is defined as R _{P − O5′} − R _{P − O2′}. In the in-line monoanionic mechanism, ζ₂ is R _{O2′ − H2′} − R _{ONB − H2′} for ζ₁ < 0.0 Å and R _{O5′ − H2′} − R _{ONB − H2′} for ζ₁ > 0.0 Å, where O_NB is for the O_1P proton transfer in (B), and for the O_2P proton transfer in (A) and (C), respectively; in the G8-assisted general base catalysis mechanism, ζ₂ is R _{O2′ − H2′} − R _{N 1 − H2′}. The units for free energies and distances are kcal/mol and Å, respectively.