Comparison of AM1 and B3LYP-DFT for inhibition of MAO-A by phenylisopropylamines: a QSAR study.

The aim of this study is to provide an initial indication regarding the scope and limitations of some state-of-the-art methods in computational chemistry, including semiempirical (AM1) and density functional theory (B3LYP), in the flip regression procedure applied to the inhibition of phenylisopropylamines. The results show that the models established based on the density functional theory-B3LYP are better than that based on semiempirical method (AM1). It is demonstrated that electron-rich ring systems and highest occupied molecular orbital levels tended to increase activity. In this contribution, it is shown that the orientation of nodes in their occupied pi orbitals, and also the energies of these orbitals explain a further large portion of the variance in their inhibitory activity.