Table 1.

Binding free energies (kcal/mol) calculated with the Molecular Mechanics/Poisson–Boltzmann (generalized Born) Surface Area (MM/PB(GB)SA) and Quantum Mechanics/generalized Born Surface Area (QM/MM-GBSA) methods. Errors labeled by the signs ± represent the standard errors of mean (SEM).

Energy Component	GIm Complex	MIm Complex
Gas term
ΔEvdW	−15.63 ± 0.06	−19.65 ± 0.05
ΔEele	−89.43 ± 0.09	−34.05 ± 0.15
ΔEMM	−105.06 ± 0.07	−53.70 ± 0.15
ΔEQM	−79.02 ± 0.08	−30.78 ± 0.13
−TΔS	11.30 ± 0.40	13.79 ± 0.32
Solvation term
PBSA
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{PBSA}\right)}^{\mathrm{ele}}$	86.43 ± 0.06	53.35 ± 0.14
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{PBSA}\right)}^{\mathrm{nonpolar}}$	−2.29 ± 0.00	−2.60 ± 0.00
ΔGsol(PBSA)	84.14 ± 0.06	50.75 ± 0.14
GBSA
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{GBSA}\right)}^{\mathrm{ele}}$	77.38 ± 0.06	42.05 ± 0.12
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{GBSA}\right)}^{\mathrm{nonpolar}}$	−3.80 ± 0.00	−3.56 ± 0.00
ΔGsol(GBSA)	73.58 ± 0.06	38.48 ± 0.12
QM-GBSA
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{QM}\text{-}\mathrm{GBSA}\right)}^{\mathrm{ele}}$	65.40 ± 0.05	34.35 ± 0.10
${\mathsf{\Delta }G}_{\mathrm{sol}\left(\mathrm{QM}\text{-}\mathrm{GBSA}\right)}^{\mathrm{nonpolar}}$	−3.80 ± 0.00	−3.56 ± 0.00
ΔGsol(QM-GBSA)	61.60 ± 0.05	30.79 ± 0.10
Binding free energy
ΔGbind(MM/PBSA)	−9.62	10.84
ΔGbind(MM/GBSA)	−20.18	−1.43
ΔGbind(QM/MM-GBSA)	−21.75	−5.85
ΔGbind(inhibition) 1 [29]	−13.00	−7.90

¹ Experimental binding free energy values, ΔG_bind(exp), were obtained using the relation of ΔG = RTlnK_i based on experimental competitive inhibition constant K_i at 303 K [29].