The electronic density obtained from a QTAIM analysis used as molecular descriptor. A study performed in a new series of DHFR inhibitors

Abstract

The results reported here indicate that the electron density obtained from a QTAIM analysis is an excellent descriptor of molecular interactions that stabilize and destabilize the formation of the ligand-receptor (L-R) complex. The study was conducted on a series of 25 compounds that have inhibitory effects on DHFR. Besides the synthesis and bioassays performed for some of these compounds, various types of molecular calculations were performed. Thus, we performed MD simulations, computations at different levels of theory (ab initio and DFT) using reduced models and a QTAIM study on the different complexes. The resulting model has allowed us to differentiate not only highly active compounds with respect to compounds weakly active, but also among compounds that have similar affinities in this series. The model also showed a high degree of predictability which allows predicting the affinity of non-synthesized compounds. Very important additional information can be obtained through this type of study, it is possible to visualize which amino acids are involved in the interactions determining the different affinities of the ligands.