Electronic Structure Analysis of Dasatinib Inhibition of Focal Adhesion Kinase

A theoretical analysis was conducted using the DFT method with the ωB97XD functional to determine the binding energies of established inhibitors and compare them to dasatinib, a kinase drug inhibitor. The quantum theoretical calculation was also used to determine the orbitals associated with these interactions. A molecular interaction pattern for FAK inhibitors was determined from these theoretical calculations. Previous literature showed that dasatinib did not exhibit any activity for FAK. Therefore, a molecular docking protocol was also applied to dasatinib in the FAK catalytic site. The results showed differences from the known inhibitors, which justified the experimental finding that dasatinib does not bind with FAK. Our results show which physicochemical properties are most important for deriving new inhibitors of the focal adhesion enzyme.