The interaction pattern between the epidermal growth factor receptor (EGFR) with a group of 4-anilinoquinazoline inhibitors has been investigated. The 3D structure of EGFR was constructed using homology modeling, and the complex structures between receptor and ligands were predicted by using molecular mechanics and molecular dynamics. From the calculations, it can be found that the van der Waals interactions, the hydrophobic interactions, as well as the H-bonding interactions are crucial for the ligand binding. The 4-phenylamino group can produce strong van der Waals adn hydrophobic interactions with the nonpolar side chains of the residues deep in the binding cleft. The R^1 and R^2 substituents on the bicyclic chromophore can also produce strong van der Waals and hydrophobic interactions with the residues located at the exterior part of the binding pocket. Moreover, the two N atoms of the quinazoline can form H-bonds with EGFR, which will produce significant contribution to biological activities. The calculated nonbonded interactions between anilinoquinazolines and EGFR, as well as the information obtained from the predicted complexes, can interpret the structure-activities of the inhibitors well, which can afford us important information for structure-based drug design.

Key words: ANILINE P, QUINAZOLINE P, INHIBITOR, NSFC