A New Approach for Drug Target and Bioactivity Prediction: The Multifingerprint Similarity Search Algorithm (MuSSeL)

We present MuSSeL, a multifingerprint similarity search algorithm, able to predict putative drug targets for a given query small molecule as well as to return a quantitative assessment of its bioactivity in terms of K_i or IC₅₀ values. Predictions are automatically made exploiting a large collection of high quality experimental bioactivity data available from ChEMBL (version 22.1) combining, in a consensus-like approach, predictions resulting from a similarity search performed using 13 different fingerprint definitions. Importantly, the herein proposed algorithm is also effective in detecting and handling activity cliffs. A calibration set including small molecules present in the last updated version of ChEMBL (version 23) was employed to properly tune the algorithm parameters. Three randomly built external sets were instead challenged for model performances. The potential use of MuSSeL was also challenged by a prospective exercise for the prediction of five bioactive compounds taken from articles published in the Journal of Medicinal Chemistry just few months ago. The paper emphasizes the importance of implementing multifingerprint consensus strategies to increase the confidence in prediction of similarity search algorithms and provides a fast and easy-to-run tool for drug target and bioactivity prediction.