Table 3.

Interactions of sample TKIs with EGFR.

Samples		EGFR-TKIs non-covalent Interactions			Ki (μM)	ΔGbind (kcal/mol)
		Hydrogen Bond	Hydrophobic	Electrostatic
THCA	EGFR-C11	Conventional 7: THR830 (1.86, 1.85 Å), ASP831 (2.16, 2.99 Å), GLU738 (1.73 Å), LYS721 (2.21, 1.66 Å). Carbon 0.	Alkyl 16: ALA719 (4.99, 3.18 Å), MET769 (5.44, 4.60 Å), LEU820 (4.17, 4.60 Å), CYS773 (4.52 Å), VAL702 (4.94, 4.10, 5.15 Å), VAL768 (4.60 Å), LEU694 (5.46 Å), LEU723 (5.06 Å), ILE735 (4.88 Å), LYS721 (5.32 Å), LEU820 (4.70 Å). π-Alkyl 2: VAL702 (4.37 Å), LYS721 (4.40 Å). π-π T-shaped 0.π-Sigma 0	π-Anion 1: ASP831 (4.70 Å)	0.4115 × 10-3	−62.807
BCP	EGFR-T15	ND	Alkyl 16: ALA719 (3.72, 3.99, 4.81 Å), VAL702 (4.77, 4.60, 3.75, 4.18 Å), LYS721 (5.32, 4.74, 4.07), MET769 (4.92, 4.45 Å), LEU820 (4.96, 4.92 Å), LEU694 (5.29 Å).	ND	2.603	−33.980
Standard drugs	EGFR-Tamoxifen	Carbon 1: ASN818 (2.93 Å)	π-Sigma 1: ALA 719 (3.73 Å). Alkyl 5: ALA719 (4.11 Å), LEU694 (4.83 Å), VAL702 (5.22 Å), MET769 (4.30 Å), LEU820 (4.84 Å) π-Alkyl 6: VAL702 (4.98, 4.58, 5.23 Å), LYS721 (4.98, 4.02 Å), LEU820 (4.89 Å). π-π T-shaped 1: PHE699 (5.13 Å).	π-Cation 2: LYS721 (4.26, 4.96 Å)	0.400	−42.098
	EGFR-Erlotinib	Conventional 4: MET769 (2.65 Å), LYS721 (1.78, 2.22, 2.06 Å). Carbon 2: ASP831 (3.51 Å), GLU738 (2.83 Å).	π-Sigma 1: 1: VAL702 (3.91 Å). π-Alkyl 9: LEU694 (5.38, 4.17, 5.45 Å), ALA719 (5.24, 4.88 Å), LEU768 (5.41 Å), LEU769 (5.06 Å), MET769 Å (4.82 Å), LEU820 (5.14 Å)	ND	0.825	−36.877
Reference flexible amino acid residues		Leu694, Val702, Ala719, Lys721, Met769, Asp776 and Leu820

ND: Not detected.

• •EGFR-THCA interactions