Table 1.

Relative and absolute binding free energies from the explicit solvent FEP simulations. All relative values were computed with respect to benzamidine (ligand A). Statistical errors are given in the parenthesis.

	A	B	C	D	E
ΔAwat	0	−25.51(0.5)	−10.55(0.5)	−1.46(0.5)	−20.93(0.7)
ΔApro	0	−23.76(0.4)	−8.74(0.3)	−1.74(0.4)	−19.60(0.6)
ΔΔAbind	0	1.75	1.81	−0.28	1.33
ΔAbind	−6.3	−4.6	−4.5	−6.6	−5.0
Experiment	−6.3,1 −6.4,2 −7.33	−4.71	−4.81	−7.0,2 −7.24	−3.8,5 −4.76
Other computation	−6.41	−7.01	−6.51	−6.14	−4.25, −2.46

¹Ref³⁹. Calculation using PB/S A combined with QM/MM.

²Ref⁴².

³Ref⁶⁶.

⁴Ref⁶⁷. Calculation using PB/SA.

⁵Ref³⁷. Non-Boltzmann thermodynamic integration (NBTI) MD simulations.

⁶Ref⁵⁹. Linear interaction energy (LIE).