A DFT-based QSAR study on inhibition of human dihydrofolate reductase

KARABULUT S., Sizochenko N., ORHAN A., Leszczynski J.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, vol.70, pp.23-29, 2016 (SCI-Expanded) identifier identifier identifier


Diaminopyrimidine derivatives are frequently used as inhibitors of human dihydrofolate reductase, for example in treatment of patients whose immune system are affected by human immunodeficiency virus. Forty-seven dicyclic and tricyclic potential inhibitors of human dihydrofolate reductase were analyzed using the quantitative structure-activity analysis supported by DFT-based and DRAGON-based descriptors. The developed model yielded an RMSE deviation of 1.1 a correlation coefficient of 0.81. The prediction set was characterized by R-2 = 0.60 and RMSE = 3.59. Factors responsible for inhibition process were identified and discussed. The resulting model was validated via cross validation and Y-scrambling procedure.