SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

TLDR

SwissTargetPrediction is an online web tool that predicts the most probable protein targets of small molecules. The 2019 version updates underlying data, retrains the model, and redefines similarity thresholds, providing a major overhaul of its backend and web interface. SwissTargetPrediction uses a similarity‑based reverse‑screening approach, searching 2D and 3D analogues among 376,342 active compounds linked to 3,068 targets, and an optimized backend returns predictions for a drug‑like molecule in 15–20 s, while the updated interface and interoperability features streamline input, analysis, and integration with other SIB tools. The updated SwissTargetPrediction retains high predictive accuracy, correctly identifying at least one human target in the top 15 predictions for over 70 % of external compounds, and is freely available at www.swisstargetprediction.ch.

Abstract

Abstract SwissTargetPrediction is a web tool, on-line since 2014, that aims to predict the most probable protein targets of small molecules. Predictions are based on the similarity principle, through reverse screening. Here, we describe the 2019 version, which represents a major update in terms of underlying data, backend and web interface. The bioactivity data were updated, the model retrained and similarity thresholds redefined. In the new version, the predictions are performed by searching for similar molecules, in 2D and 3D, within a larger collection of 376 342 compounds known to be experimentally active on an extended set of 3068 macromolecular targets. An efficient backend implementation allows to speed up the process that returns results for a druglike molecule on human proteins in 15–20 s. The refreshed web interface enhances user experience with new features for easy input and improved analysis. Interoperability capacity enables straightforward submission of any input or output molecule to other on-line computer-aided drug design tools, developed by the SIB Swiss Institute of Bioinformatics. High levels of predictive performance were maintained despite more extended biological and chemical spaces to be explored, e.g. achieving at least one correct human target in the top 15 predictions for >70% of external compounds. The new SwissTargetPrediction is available free of charge (www.swisstargetprediction.ch).