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

RODRIGO D. TOSSO; MARCELA VETTORAZZI; SEBASTIAN A. ANDUJAR; LUCAS J. GUTIERREZ; JUAN C. GARRO MARTÍNEZ; EMILIO ANGELINA

JOURNAL OF MOLECULAR STRUCTURE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 1134 p. 464 - 474

0022-2860

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