Table I.

Observed and calculated reaction free energies (ΔG⁰) and activation free energies (ΔG^≠) of the uncatalyzed reaction in water and HIV-1 protease.^c

System	$\Delta G_{obs}^{\#}({\Psi }_1\to {\psi }_3)$	$\Delta G_{obs}^0({\Psi }_1\to {\psi }_2)$	$\Delta G_{obs}^{\#}({\Psi }_2\to {\psi }_3)$	$\Delta G_{calc}^{\#}({\Psi }_1\to {\psi }_3)$	$\Delta G_{calc}^0({\Psi }_1\to {\psi }_2)$	$\Delta G_{calc}^{\#}({\Psi }_2\to {\psi }_3)$
watera	33.0	15.0	18.0	32.8	14.7	18.1
HIV-1 proteaseb	17.0	11.0	6.0	19.1	11.8	7.3

^aThe experimental information of the uncatalyzed reaction in water are taken from Ref¹⁵.

^bThe experimental information of the reaction in protein are taken from Ref⁵¹.

^cThe EVB parameters used in calculations are described in the Table SI and Table SII (see SI). ψ₁,ψ₂ and ψ₃ designates the reactant state (RS), the TS1 and the intermediate (Int) respectively (See Figure 2).