ONIOM Study of Binding Affinity of Breast Cancer Imine Drugs to Estrogen Receptor-α

We used computational method of ONIOM to obtain drug binding energy. Three-layer ONIOM (M06-2x/6-31+G*:PM6: AMBER) method was used for studying of drug binding. Initial models were constructed using binding sites derived from Hotspot Wizard Server and capping of their amino acids. Binding energy values demonstrated that strongest binding belong to drug of 4,4 -((o-tolylimino)methylene)diphenol and weakest binding happen with drug of 4,4 -(((2-chlorophenyl)imino)methylene)diphenol. Also, we have found that binding energy depend on substitute group on studied drugs. Interaction energy data showed that drug binding strength depend on hydrogen bonding with residues of Glu353, Arg394 and Thr347 and also hydrophobic interaction with other residues.

Keywords:

Cancer , Binding energy , DFT