Ranking-Oriented Quantitative Structure–Activity Relationship Modeling Combined with Assay-Wise Data Integration

Abstract

In ligand-based drug design, quantitative structure–activity relationship (QSAR) models play an important role in activity prediction. One of the major end points of QSAR models is half-maximal inhibitory concentration (IC50). Experimental IC50 data from various research groups have been accumulated in publicly accessible databases, providing an opportunity for us to use such data in predictive QSAR models. In this study, we focused on using a ranking-oriented QSAR model as a predictive model because relative potency strength within the same assay is solid information that is not based on any mechanical assumptions. We conducted rigorous validation using the ChEMBL database and previously reported data sets. Ranking support vector machine (ranking-SVM) models trained on compounds from similar assays were as good as support vector regression (SVR) with the Tanimoto kernel trained on compounds from all the assays. As effective ways of data integration, for ranking-SVM, integrated compounds should be selected from only similar assays in terms of compounds. For SVR with the Tanimoto kernel, entire compounds from different assays can be incorporated.