Structure–activity relationship study of trifluoromethylketone inhibitors of insect juvenile hormone esterase: Comparison of several classification methods

Juvenile hormone esterase (JHE) plays a key role in the development and metamorphosis of holometabolous insects. Its inhibitors could possibly be targeted for insect control. Conversely, JHE may also be involved in endocrine disruption by xenobiotics, resulting in detrimental effects in beneficial insects. There is therefore a need to know the structural characteristics of the molecules able to monitor JHE activity, and to develop SAR and QSAR studies to estimate their effectiveness. For a large diverse population of 181 trifluoromethylketones (TFKs) – the most potent JHE inhibitors known to date – we recently proposed a binary classification (active/inactive) using a support vector machine and Codessa structural descriptors. We have now examined, using the same data set and with the same descriptors, the applicability and performance of five other machine learning approaches. These have been shown able to handle high dimensional data (with descriptors possibly irrelevant or redundant) and to cope with co...