Table 2.

Binding free energies of the selected inhibitor-bound complexes (CYP3A4-YK1 toCYP3A4-YK5) from Monte Carlo calculations in WaterSwap, MM/PBSA and MM/GBSA. Note that two different WaterSwap calculations (using centroid clusters c0 and c1) were performed for YK4 and YK5 as the dominant cluster did not include structures from the entire simulation.

Inhibitor-Bound Complex					WaterSwap
	IC50 nM	Autodock Score kcal/mol	MM/PBSA kcal/mol	MM/GBSA kcal/mol	BAR kcal/mol	FEP kcal/mol	TI kcal/mol	Average kcal/mol
CYP3A4-YK1	0.1	−9.9	−40.78 ± 0.43	−61.22 ± 0.43	−41.1	−40.2	−40.6	−40.6 ± 0.5
CYP3A4-YK2	0.4	−11.6	−25.50 ± 0.33	−37.44 ± 0.24	−37.5	−36.8	−37.7	−37.3 ± 0.5
CYP3A4-YK3	10	−9.5	−32.37 ± 0.31	−49.48 ± 0.31	−47.3	−46.3	−46.5	−46.7 ± 0.5
CYP3A4-YK4	2.6	−11.7	−30.87 ± 0.31	−34.96 ± 0.23	−40.3	−39.5	−39.3	−39.7 ± 0.5
					−31.6	−30.6	−30.5	−30.9 ± 0.6
CYP3A4-YK5	38	−10.4	−22.52 ± 0.34	−38.46 ± 0.25	−36.1	−36.3	−35.6	−36.0 ± 0.4
					−40.4	−39.8	−39.9	−40.0 ± 0.3