Application of ab initio theory to QSAR study of 1,4-dihydropyridine-based calcium channel blockers using GA-MLR and PC-GA-ANN procedures.

The usefulness of the quantum chemical descriptors, calculated at the level of the RHF theory using 6-31G basis set for QSAR study of 1,4-dihydropyridine-based calcium channel antagonist was examined. A data set containing 45 dihydropyridine derivatives with known activity was used. Multiple linear regressions combined with genetic algorithm for variable selection and an artificial neural network model combined with principal component analysis for dimension reduction and genetic algorithm for factor selection (PC-GA-ANN) were employed. Some multiparametric MLR equations with good statistical quality were obtained for different classes of dihydropyridine derivatives. The resulting equations suggest that the electronic properties of the atoms belonging to the backbone of the molecules as well as the conformation of the molecules affect the binding of these molecules with their receptor. In the PC-GA-ANN, The principal components of the descriptors data matrix were used as the input of the neural network and then genetic algorithm was applied to select the most relevant set of principal components. Two ANN models with five selected principal components were obtained. These models, which have high statistical qualities, can predict the activity of the molecules with prediction errors lower than +/-5%. Copyright 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1495-1503, 2004