QSAR Study of 17β-HSD3 Inhibitors by Genetic Algorithm-Support Vector Machine as a Target Receptor for the Treatment of Prostate Cancer.

Abstract

The 17β-HSD3 enzyme plays a key role in treatment of prostate cancer and small inhibitors can be used to efficiently target it. In the present study, the multiple linear regression (MLR), and support vector machine (SVM) methods were used to interpret the chemical structural functionality against the inhibition activity of some 17β-HSD3inhibitors. Chemical structural information were described through various types of molecular descriptors and genetic algorithm (GA) was applied to decrease the complexity of inhibition pathway to a few relevant molecular descriptors. Non-linear method (GA-SVM) showed to be better than the linear (GA-MLR) method in terms of the internal and the external prediction accuracy. The SVM model, with high statistical significance (R2train = 0.938; R2test = 0.870), was found to be useful for estimating the inhibition activity of 17β-HSD3 inhibitors. The models were validated rigorously through leave-one-out cross-validation and several compounds as external test set. Furthermore, the external predictive power of the proposed model was examined by considering modified R2 and concordance correlation coefficient values, Golbraikh and Tropsha acceptable model criteria's, and an extra evaluation set from an external data set. Applicability domain of the linear model was carefully defined using Williams plot. Moreover, Euclidean based applicability domain was applied to define the chemical structural diversity of the evaluation set and training set.