Investigation of the interactions of anticancer drugs with tyrosine kinase enzyme using semi-empirical methods and comparisons with DFT Calculations

In this work, the interaction energies of some commercial molecules that are still used clinically with aminoacids in the active region of the tyrosine kinase were calculated by semi-empirical methods such as AM1 and PM3. There are already some results calculated with DFT methods and published in an article previously. By comparing the results there with those found here, it has been discussed whether semi-empirical methods with much shorter computation times can be used to estimate the most critical aminoacids for the tyrosine kinase enzyme instead of DFT methods which take much more time. According to the results obtained here, in order for semi-empirical methods to be used instead of DFT methods for this purpose, the examined ligands must have an electrical charge in the physiological environment. In other words, the hypothesis put forward remains valid only if the ligand under consideration has a charge. The use of semi-empirical methods such as AM1 and PM3 instead of DFT methods to estimate the residues with which a molecule that does not have any electrical charge interacts most strongly did not yield overlapping results.