Table 1.

Calculated and experimental binding energy changes for known resistance mutations of HIV-1 protease

Mutations	PI	ΔEbind (calc), kcal/mole	ΔEvwa	ΔEhba	ΔEela	Fold resistanceb	ΔEbind (exptl), kcal/molec	Reference
G48V	SQV	3.5	2.1	0.5	0.5	160	3.1	Maschera et al. 1996
I50V	SQV	2.2	1.9	0.3	0.1	21	1.9	Markland et al. 2000
	APV	2.9	2.9	0.1	0.1	83	2.7	Markland et al. 2000
M46I/I47V/I50V	APV	3.6	1.5	1.8	0.4	270	3.4	Partaledis et al. 1995
M46I/G48V/I50V/I84L	SQV	3.8	1.6	1.3	0.6	300	3.5	Markland et al. 2000
	APV	0.9	1.0	−0.2	−0.1	2	0.4	Markland et al. 2000
V82A	IDV	1.8	1.2	0.0	0.5	22	1.9	Gulnik et al. 1995
	RTV	2.4	2.8	0.2	−0.5	10	1.4	Gulnik et al. 1995
I84V	SQV	2.2	2.1	−0.1	0.1	12	1.5	Partaledis et al. 1995
	APV	2.0	2.0	0.0	0.1	23	1.9	Partaledis et al. 1995
	IDV	1.5	1.0	0.0	0.4	20	1.8	Partaledis et al. 1995
V32I/I84V	IDV	2.9	2.2	0.2	0.2	80	2.7	Gulnik et al. 1995
	RTV	2.0	1.7	0.2	0.1	64	2.6	Gulnik et al. 1995
V82T/I84V	IDV	2.4	1.9	0.0	0.3	59	2.5	Schock et al. 1996
	RTV	2.9	2.6	0.1	0.0	158	3.1	Schock et al. 1996
M46I/I84V	NFV	1.7	1.5	−0.1	0.2	5–30d		Patick et al. 1996
D30N	NFV	1.5	−0.9	1.6	0.8	7d		Patick et al. 1996
L10F/V32I/M46I/ I47V/I84V	LPV	2.9	3.3	−0.3	−0.3	25–100	2.0–2.8	Carrillo et al. 1998

^a ΔE_vw, ΔE_hb, and ΔE_el are changes in the van der Waals, hydrogen bonding, and electrostatic components of binding energy (see equation 2 in Materials and Methods).

^b Fold changes in K_i or IC₅₀ values.

^c ΔE_bind(exptl) was calculated using equations 4 or 5 in Materials and Methods.

^d Ratios of EC₉₀ values; experimental binding energies were not estimated.