QSAR studies of the bioactivity of hepatitis C virus (HCV) NS3/4A protease inhibitors by multiple linear regression (MLR) and support vector machine (SVM)

Abstract In this study, quantitative structure-activity relationship (QSAR) models using various descriptor sets and training/test set selection methods were explored to predict the bioactivity of hepatitis C virus (HCV) NS3/4A protease inhibitors by using a multiple linear regression (MLR) and a support vector machine (SVM) method. 512 HCV NS3/4A protease inhibitors and their IC 50 values which were determined by the same FRET assay were collected from the reported literature to build a dataset. All the inhibitors were represented with selected nine global and 12 2D property-weighted autocorrelation descriptors calculated from the program CORINA Symphony. The dataset was divided into a training set and a test set by a random and a Kohonen’s self-organizing map (SOM) method. The correlation coefficients (r 2 ) of training sets and test sets were 0.75 and 0.72 for the best MLR model, 0.87 and 0.85 for the best SVM model, respectively. In addition, a series of sub-dataset models were also developed. The performances of all the best sub-dataset models were better than those of the whole dataset models. We believe that the combination of the best sub- and whole dataset SVM models can be used as reliable lead designing tools for new NS3/4A protease inhibitors scaffolds in a drug discovery pipeline.