Figure 8.

Folding free energy surfaces for 10 μM (solid line) and 100 nM (dotted line) HIV-protease under native conditions (0 M urea) and for 10 μM (dashed line) HIV-PR* under unfolding conditions (4 M urea). The free energies were calculated for the 2U ⇆ 2M ⇆ N₂ model using a dimeric reference state and the parameters listed in Table 1. The activation free energies for the transition states, ΔG^o‡, were calculated from the rate constant, k, using the Kramers formalism, ΔG^o=−RTln(k/k_o), where R is the gas constant, T is the absolute temperature and k_o is the Kramers prefactor. The activation energy depends upon the estimate of the prefactor and is somewhat arbitrary. The Kramers prefactor value of 1×10⁸ s⁻¹ used here is considered to be a reasonable estimate.⁵⁴ The abscissa describes the reaction coordinate and is depicted as the Tanford β value, β_T. The abscissa is normalized to the total change in the m value for the folding reaction from 2U to N₂, 2.50 kcal (mol dimer)⁻¹ M⁻¹ (Table 1).