Predicting CNS permeability of drug molecules: comparison of neural network and support vector machine algorithms.

Two different machine-learning algorithms have been used to predict the blood-brain barrier permeability of different classes of molecules, to develop a method to predict the ability of drug compounds to penetrate the CNS. The first algorithm is based on a multilayer perceptron neural network and the second algorithm uses a support vector machine. Both algorithms are trained on an identical data set consisting of 179 CNS active molecules and 145 CNS inactive molecules. The training parameters include molecular weight, lipophilicity, hydrogen bonding, and other variables that govern the ability of a molecule to diffuse through a membrane. The results show that the support vector machine outperforms the neural network. Based on over 30 different validation sets, the SVM can predict up to 96% of the molecules correctly, averaging 81.5% over 30 test sets, which comprised of equal numbers of CNS positive and negative molecules. This is quite favorable when compared with the neural network's average performance of 75.7% with the same 30 test sets. The results of the SVM algorithm are very encouraging and suggest that a classification tool like this one will prove to be a valuable prediction approach.