Combining DFT and QSAR computation to predict the interaction of flavonoids with the GABA (A) receptor using electronic and topological descriptors

To establish a quantitative structure-activity relationship model of the binding affinity constants (−log Ki) of 41 flavonoid derivatives towards the GABA (A) receptor, the DFT-B3LYP method with basis set 6-31G (d) was performed to gain insights into the chemical structure and property information for the studied compounds. The best topological and electronic descriptors were selected. This work was conducted with principal component analysis (PCA), multiple linear regression (MLR), multiple non-linear regression (MNLR) and artificial neural network (ANN). According to these analyses, we propose quantitative models and interpret the activity of the compounds based on multivariate statistical analysis. The statistical results of the MLR, MNLR and ANN indicate that the determination coefficients R2 were 0.896, 0.925 and 0.916, respectively. The results show that the three modelling methods can predict the studied activity well and may be useful for predicting the biological activity of new compounds. The statistical results indicate that the models are statistically significant and stable with data variation in the external validation.