Simple graph-theoretical model for flavonoid binding to P-glycoprotein

Abstract

Three sets of flavonoid derivatives (N=32, 40, and 74) and logarithms of their dissociation constants (K_d) that describe flavonoid affinity toward P-glycoprotein were modelled using five connectivity indices. The best results were obtained with the zero-order valence molecular connectivity index (⁰χ^v) for all three sets. Standard errors of the calibration models were around 0.3, and of the constants from the test sets even a little lower, 0.22 and 0.24. Despite using only one descriptor, our model proved better in internal (cross-validation) and especially in external (test set) statistics than much more demanding methods used in previous 3D QSAR modelling.