Table 2.

Comparison of experimental and computed free energy difference for the ACK1 inhibitors.

Parent cmpd/Transformation	ΔΔGexp	ΔΔGFEPa	ΔΔGSSFEPb	ΔΔGLGFEc	ΔΔGLGFEd
L1/1➔2	1.28	1.97±0.40	3.00±0.22	0.57±0.32	1.09
L1/2➔3	2.71	−1.02±0.18	4.32±1.20	2.17±0.32	2.25
L1/1➔3	3.98	0.96±0.51	7.32±1.18	2.74±0.53	3.33
L2/4➔5e	−3.76	1.29±1.58	4.53±3.21	1.25±1.66	0.74
L3/6➔7	−0.95	0.93±0.19	0.37±0.54	−0.91±0.11	−0.75
L4/8➔9	−0.87	0.77±0.29	2.00±0.99	−0.56±0.42	−0.74
L5/10➔11	0.57	0.45±0.34	0.17±1.47	0.55±0.31	0.50
L5/10➔12	0.11	0.60±0.22	2.22±0.84	−0.11±0.26	−0.03
	R2	0.11	0.18	0.33	0.52
	PI	−0.25	0.27	0.52	0.60
	RMSD	2.63	3.54	1.86	1.62
	AAD	2.08	2.71	1.01	0.79
Omit Outliere	R2	0.05	0.78	0.98	1.00
	PI	0.06	0.85	1.00	0.99
	RMSD	2.07	2.11	0.59	0.33
	AAD	1.65	1.90	0.44	0.26

^aAverage and standard deviations (n=3) from the standard FEP calculations.

^bAverage and standard deviations (n=5) from the single-step FEP calculations.

^cAverage and standard deviations (n=5) from the MC SILCS/LGFE calculations.

^dMinimum energy conformation from the MC SILCS/LGFE calculations.

^eL2/4➔5 (2H to 2Cl)outlier omitted from the second statistical analysis.