Binding free energies of inhibitors to EGFR calculated by MM-PBSA method^a.

Energy	TAK-285		W2P		HKI-272
	WT	T790M/L858R	WT	T790M/L858R	WT	T790M/L85R
ΔEele	−30.59 ± 4.06	−20.23 ± 4.42	−30.16 ± 4.33	−28.26 ± 4.91	−23.05 ± 4.12	−17.86 ± 4.15
ΔEvdw	−62.49 ± 2.64	−56.14 ± 2.60	−60.41 ± 2.76	−55.63 ± 2.28	−61.71 ± 2.68	−59.64 ± 2.38
ΔGpol	60.61 ± 5.07	49.58 ± 5.01	58.38 ± 4.99	57.29 ± 3.62	51.04 ± 5.53	49.28 ± 4.87
ΔGnonpol	−7.13 ± 0.13	−6.53 ± 0.31	−7.34 ± 0.16	−6.89 ± 0.05	−7.43 ± 0.33	−7.50 ± 0.32
bΔGele+pol	30.02 ± 3.56	29.36 ± 3.38	28.22 ± 3.15	29.03 ± 3.01	27.99 ± 3.22	31.42 ± 3.83
−TΔS	22.43 ± 4.15	21.76 ± 4.18	22.91 ± 4.13	21.80 ± 3.79	22.93 ± 4.03	21.47 ± 3.99
cΔGbind	−17.17	−11.56	−16.62	−11.69	−18.22	−14.25
dΔGexp	−11.54	−6.97	−11.45	−7.00	−11.82	−9.87

^aAll values are in kcal mol⁻¹.

^bΔG_ele+pol = ΔE_ele + ΔG_pol.

^cΔG_bind = ΔE_ele + ΔE_vdw + ΔG_pol + ΔG_nonpol − TΔS.

^dThe experimental values were derived from the experimental IC₅₀ values using the equation ΔG_exp = −TR ln IC₅₀. In this calculation, the nonlinear regression analysis of the percentage inhibitions was used to compute the IC50 mentioned in ref. 29.