The application of machine learning methods to the prediction of novel ligands for RORy/RORyT receptors

In this work, we developed and applied a computational procedure for creating and validating predictive models capable of estimating the biological activity of ligands. The combination of modern machine learning methods, experimental data, and the appropriate setup of molecular descriptors led to a set of well-performing models. We thoroughly inspected both the methodological space and various possibilities for creating a chemical feature space. The resulting models were applied to the virtual screening of the ZINC20 database to identify new, biologically active ligands of RORy receptors, which are a subfamily of nuclear receptors. Based on the known ligands of RORy, we selected candidates and calculate their predicted activities with the best-performing models. We chose two candidates that were experimentally verified. One of these candidates was confirmed to induce the biological activity of the RORy receptors, which we consider proof of the efficacy of the proposed methodology.