Table III.

Calculated and Experimentaly observed Vitality values for Mutant Proteases.^a

Inhibitor	Mutation	Ki (inhibitor)		kcat/KM (substrate TS)						Vitality
		$\Delta G_{bind}^{exp}\left(drug\right)$	$\Delta G_{bind}^{calc}\left(drug\right)$ (fitted; β = 0.26)	$\Delta G_{bind}^{exp}\left(TS\right)$	$\Delta G_{bind}^{calc}\left(TS\right)$	$\Delta \Delta G_{bind}^{exp}\left(drug\right)$	$\Delta \Delta G_{bind}^{exp}\left(TS\right)$	$\Delta \Delta G_{bind}^{calc}\left(drug\right)$	$\Delta \Delta G_{bind}^{calc}\left(TS\right)$	(γM / γN)exp	(γM / γN)calc
Saquinavir	WT	−13.39	−13.69	−13.53	−13.34	-	-	-	-	-	-
	V82A	−13.09	−12.48	−13.61	−13.49	−0.3	0.08	−0.91	0.15	0.53	0.17
	V82F	−12.68	−12.16	−13.63	−13.63	−0.71	0.1	−1.23	0.29	0.25	0.08
	I84V	−11.99	−12.07	−12.73	−12.63	−1.4	−0.8	−1.32	−0.71	0.36	0.36
Ritonavir	WT	−13.32	−12.7	−13.53	−13.34	-	-	-	-	-	-
	V82A	−11.89	−11.66	−13.61	−13.49	−1.43	0.08	−1.04	0.15	0.08	0.13
	V82F	−13.44	−13.01	−13.63	−13.63	0.12	0.1	0.31	0.29	1.03	1.03
	I84V	−11.86	−11.93	−12.73	−12.63	−1.46	−0.8	−0.77	−0.71	0.33	0.9
Indinavir	WT	−13.44	−12.54	−13.53	−13.34	-	-	-	-	-	-
	V82A	−12.34	−12.2	−13.61	−13.49	−1.1	0.08	−0.34	0.15	0.14	0.44
	V82F	−13.94	−13.05	−13.63	−13.63	0.5	0.1	0.51	0.29	1.97	1.45
	I84V	−12.88	−11.76	−12.73	−12.63	−0.56	−0.8	−0.78	−0.71	1.50	0.89
DMP323	WT	−12.37	−12.19	−13.53	−13.34	-	-	-	-	-	-
	V82A	−11.09	−11.54	−13.61	−13.49	−1.28	0.08	−0.65	0.15	0.10	0.26
	V82F	−12.72	−12.74	−13.63	−13.63	0.35	0.1	0.55	0.29	1.53	1.55
	I84V	−10.59	−10.73	−12.73	−12.63	−1.78	−0.8	−1.46	−0.71	0.19	0.28
SD146	WT	−13.63	−13.23	−13.53	−13.34	-	-	-	-	-	-
	V82A	−13.53	−13.38	−13.61	−13.49	−0.1	0.08	0.15	0.15	0.74	1
	V82F	−14.04	−13.93	−13.63	−13.63	0.41	0.1	0.70	0.29	1.69	2
	I84V	−13.07	−13.09	−12.73	−12.63	−0.56	−0.8	−0.14	−0.71	1.50	2.62
XV638	WT	−13.58	−13.18	−13.53	−13.34	-	-	-	−	-	-
	V82A	−13.53	−12.92	−13.61	−13.49	−0.05	0.08	−0.26	0.15	0.80	0.5
	V82F	−13.94	−13.65	−13.63	−13.63	0.36	0.1	0.47	0.29	1.55	1.36
	I84V	−13.53	−13.13	−12.73	−12.63	−0.05	−0.8	−0.05	−0.71	3.56	3.05

^aAll values in kcal/mol. $\Delta G_{bind}^{exp}\left(drug\right)$ and $\Delta G_{bind}^{exp}\left(TS\right)$ are the binding free energies of the inhibitor and substrate transition state, respectively (derived from the experimental K_i reported in Ref⁵¹). $\Delta G_{bind}^{calc}\left(drug\right)$ and $\Delta G_{bind}^{calc}\left(TS\right)$ are the calculated binding free energies of the inhibitor and the substrate transition state, respectively, calculated using our PDLD/S-LRA/β method.