Prediction of Anti-proliferation Effect of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives by Random Forest and Mix-Kernel Function SVM with PSO

Abstract

In order to predict the anti-gastric cancer effect of [1,2,3]triazolo[4,5-d]pyrimidine derivatives (1,2,3-TPD), quantitative structure–activity relationship (QSAR) studies were performed. Based on five descriptors selected from descriptors pool, four QSAR models were established by heuristic method (HM), random forest (RF), support vector machine with radial basis kernel function (RBF-SVM), and mix-kernel function support vector machine (MIX-SVM) including radial basis kernel and polynomial kernel function. Furthermore, the model built by RF explained the importance of the descriptors selected by HM. Compared with RBF-SVM, the MIX-SVM enhanced the generalization and learning ability of the constructed model simultaneously and the multi parameters optimization problem in this method was also solved by particle swarm optimization (PSO) algorithm with very low complexity and fast convergence. Besides, leave-one-out cross validation (LOO-CV) was adopted to test the robustness of the models and Q² was used to describe the results. And the MIX-SVM model showed the best prediction ability and strongest model robustness: R² = 0.927, Q² = 0.916, mean square error (MSE) = 0.027 for the training set and R² = 0.946, Q² = 0.913, MSE = 0.023 for the test set. This study reveals five key descriptors of 1,2,3-TPD and will provide help to screen out efficient and novel drugs in the future.