QSAR study of HCV NS5B polymerase inhibitors using the genetic algorithm-multiple linear regression (GA-MLR)

摘要

Quantitative structure–activity relationship (QSAR) study has been employed for predicting the inhibitory activities of the Hepatitis C virus (HCV) NS5B polymerase inhibitors. A data set consisted of 72 compounds was selected, and then different types of molecular descriptors were calculated. The whole data set was split into a training set (80 % of the dataset) and a test set (20 % of the dataset) using principle component analysis. The stepwise (SW) and the genetic algorithm (GA) techniques were used as variable selection tools. Multiple linear regression method was then used to linearly correlate the selected descriptors with inhibitory activities. Several validation technique including leave-one-out and leave-group-out cross-validation, Y-randomization method were used to evaluate the internal capability of the derived models. The external prediction ability of the derived models was further analyzed using modified r2, concordance correlation coefficient values and Golbraikh and Tropsha acceptable model criteria's. Based on the derived results (GA-MLR), some new insights toward molecular structural requirements for obtaining better inhibitory activity were obtained.