TABLE 2.

Binding thermodynamic parameters for NFV, DRV, and APV binding to AE and clade B variants^a

Inhibitor and protease variant	Ka (M−1)	Kd (nM)	Kd ratio	ΔH (kcal mol−1)	ΔΔH	−TΔS (kcal mol−1)	Δ(−TΔS)	ΔG (kcal mol−1)	ΔΔG
NFV
B-WT	(2.6 ± 0.5) × 109	0.39 ± 0.07	1.0	4.4 ± 0.1		−17.0		−12.6 ± 0.1
B-D30N/N88D	(1.2 ± 0.4) × 108	8.1 ± 2.8	20.7	6.7 ± 0.3	2.3	−17.5	0.5	−10.8 ± 0.2	1.8
AE-WT	(3.7 ± 1.0) × 108	2.7 ± 0.7	6.9	5.0 ± 0.3	0.6	−16.6	0.9	−11.5 ± 0.2	1.1
AE-N88S	(5.8 ± 1.2) × 107	17.2 ± 3.5	44.1	6.2 ± 0.7	1.8	−16.6	0.9	−10.4 ± 0.1	2.2
DRV
B-WT	(2.2 ± 1.1) × 1011	0.004 ± 0.002	1.0	−12.1 ± 0.9		−3.1		−15.2 ± 0.3
B-D30N/N88D	(3.7 ± 0.7) × 1010	0.026 ± 0.005	6.5	−12.5 ± 0.4	−0.4	−1.6	1.5	−14.2 ± 0.1	1.0
AE-WT	(9.1 ± 0.3) × 1010	0.0109 ± 0.0003	2.7	−10.1 ± 0.5	2.0	−4.6	−1.5	−14.7 ± 0.02	0.5
AE-N88S	(1.1 ± 0.8) × 1010	0.087 ± 0.062	21.8	−5.1 ± 3.6	7.0	−8.4	−5.3	−13.5 ± 0.4	1.7
APV
B-WT	(2.6 ± 1.3) × 109	0.39 ± 0.20	1.0	−7.3 ± 0.9		−5.3		−12.6 ± 0.3
B-D30N/N88D	(1.2 ± 0.2) × 1010	0.08 ± 0.01	0.2	−10.2 ± 1.5	−2.9	−3.3	2.0	−13.5 ± 0.09	−0.9
AE-WT	(3.1 ± 0.2) × 109	0.32 ± 0.02	0.8	−5.5 ± 0.3	−1.8	−7.3	−2.0	−12.70 ± 0.03	−0.1
AE-N88S	(1.3 ± 0.9) × 1010	0.08 ± 0.06	0.2	−5.0 ± 3.6	2.3	−8.6	−3.3	−13.6 ± 0.4	−1.0

^aK_a, association constant; K_d, dissociation constant; H, enthalpy; T, temperature; S, entropy; G, Gibbs free energy.