3.4. Molecular Modeling

Docking studies were carried out on AutoDock 4.2 (The Scripps Research Institute, MB-5, y, La Jolla, CA, USA). The crystal structure (PDB: 3IKA) of the kinase domain of EGFR^T790M bound to inhibitor 3 was used in the docking studies. The enzyme preparation and the hydrogen atoms addition was performed in the preparation process. The whole EGFR enzyme was defined as a receptor and the site sphere was selected on the basis of the binding location of WZ4002. By moving WZ4002 and the irrelevant water, molecule DY3002 was placed. The binding interaction energy was calculated to include Van der Waals, electrostatic, and torsional energy terms defined in the tripos force field. The structure optimization was performed using a genetic algorithm, and only the best-scoring ligand protein complexes were kept for analyses. The WWW site also includes many resources for use of AutoDock, including detailed tutorials that guide users through basic AutoDock usage, docking with flexible rings, and virtual screening with AutoDock. Tutorials may be found at: http://autodock.scripps.edu/faqs-help/tutorial.