Table 2.

Activity of compounds on different structural properties of EGFR and its mutants as ATP competitive inhibitors. The binding free energy is given in Kcal/mol and the distances are in Å.

EGFR Mutants		exon19del		EGFR_L858R		Wildtype EGFR
Inhibitor	Properties	Chain A	Chain B	Chain A	Chain B	Chain A	Chain B
Erlotinib	Binding Energy of inhibitor	−46.61	−36.29	−63.30	−56.41	−62.06	−40.37
	Binding Energy of ATP	−35.92	−32.26	−38.51	−37.26	−38.94	−56.57
	DFG motif and αC-helix orientation *	Out	In	In	In	In	In
	Distance between Lys745 and Glu762	3.6 and 3.1	3.4 and 3.2	3.9 and 2.8	9.6 and 6.4	6.4 and 4.7	6.5 and 7.5
	Downward movement of P loop	No	Yes	Yes	No	No	Yes
CAPE	Binding Energy of inhibitor	−38.15	− 58.83	−45.43	−49.22	−65.68	−63.23
	Binding Energy of ATP	−37.61	−34.63	−26.92	−23.62	−58.39	−30.15
	DFG motif and αC-helix orientation *	In	In	In	In	In	In
	Distance between Lys745 and Glu762	3.6 and 3.5	3.4 and 3.7	3.9 and 3.1	9.6 and 6.5	6.4 and 3.9	6.5 and 10.1
	Downward movement of P loop	Yes	yes	Yes	Yes	No	Yes
Wi-A	Binding Energy of inhibitor	−49.35	−46.23	−22.52	−44.50	−49.50	−48.78
	Binding Energy of ATP	−45.06	−30.59	−56.43	−62.40	−35.78	−35.78
	DFG motif and αC-helix orientation *	In	In	In	In	In	In
	Distance between Lys745 and Glu762	3.6 and 3.4	3.4 and 3.2	3.9 and 3.1	9.6 and 6.4	6.4 and 3.5	6.5 and 6.4
	Downward movement of P loop	No	No	No	No	No	Yes
Wi-N	Binding Energy of inhibitor	−59.83	−22.21	−45.76	−51.86	−44.88	−51.70
	Binding Energy of ATP	−14.15	−23.45	−20.82	−20.29	−35.42	−37.25
	DFG motif and αC-helix orientation *	In	In	In	In	In	In
	Distance between Lys745 and Glu762	3.6 and 3.6	3.4 and 3.2	3.9 and 3.7	9.6 and 6.4	6.4 and 3.3	6.5 and 7.8
	Downward movement of P loop	Yes	Yes	Yes	Yes	No	No

* ‘In’ refers to DFG and αC-helix inward conformation; ‘Out’ refers to DFG and αC-helix outward conformation.