Theoretical Study and Principal Component Analysis of Focal Adhesion Kinase Inhibitors

DFT functionals, M06 and B3LYP, with the 6-31G(d) and LANL2DZ basis sets were used to study pyrrolopyrimidines as focal adhesion kinase (FAK) inhibitors. Thermochemistry was studied at the semi-empirical PM6 level. A set of seven molecules derived from pyrrolopyrimidine of known activity was evaluated. HOMO and LUMO orbitals were investigated for all inhibitors to understand the importance of frontier molecular orbitals for the activity. Molecular electrostatic potential maps helped in the analysis of the interaction between the amino acids in the catalytic site and their inhibitors. Interaction energies and entropic factors were also computed. Principal component analysis was performed to study the activity and their relations with theoretical properties. Theoretical results suggested the importance of electron density close to the Cys502 residue for the experimental activity.