Table 1.

Binding free energy difference $\Delta \Delta G^{\text{binding}}=\Delta G_{\mathit{mut}}^{\text{binding}}-\Delta G_{\mathit{WT}}^{\text{binding}}$(kcal/mol).

Simulation	Energy	Rep1	Rep2	Rep3	Rep4	Rep5	Average	ΔΔGtheor	$\Delta \Delta G_{\mathit{theor}}^{\mathit{avg}}$	ΔΔGexp
FGFR1V561M with PD173074
Forward	$\Delta G_{\text{protein}}^{\mathit{alch}}$	1.03	0.46	1.08	0.60	0.96	0.83	3.66	3.25	2.73
	$\Delta G_{\text{complex}}^{\mathit{alch}}$	−2.90	−2.28	−3.28	−3.07	−2.63	−2.83		(0.42)	(0.18)
Reverse	$\Delta G_{\text{protein}}^{\mathit{alch}}$	0.73	0.51	0.77	1.31	0.97	0.86	2.83
	$\Delta G_{\text{complex}}^{\mathit{alch}}$	−2.35	−1.54	−1.95	−1.70	−2.31	−1.97
FGFR1V561M with TKI258
Forward	$\Delta G_{\text{protein}}^{\mathit{alch}}$	1.03	0.46	1.08	0.60	0.96	0.83	−0.43	−0.55	−0.60
	$\Delta G_{\text{complex}}^{\mathit{alch}}$	0.68	1.18	1.53	1.69	1.20	1.26		(0.12)	(1.14)
Reverse	$\Delta G_{\text{protein}}^{\mathit{alch}}$	0.73	0.51	0.77	1.31	0.97	0.86	−0.66
	$\Delta G_{\text{complex}}^{\mathit{alch}}$	1.48	1.39	1.84	0.66	2.22	1.52

Values in parentheses are uncertainties of the binding free energy changes. For calculation, they are simply half the differences of the forward and reverse results, while for the experiment, they are standard deviations of repeated measurements.