We previously introduced the Gaussian Ensemble Screening (GES) approach to predict relationships between drug classes rapidly without requiring thousands of bootstrap comparisons as in current promiscuity prediction approaches [1]. Here, we present the GES polypharmacology fingerprint: the first fingerprint which codifies promiscuity information. It can be calculated for any ligand. Its length is variable and corresponds to the desired number of targets for which the promiscuity is investigated. The similarity between the 3D shapes and chemistry of ligands is measured with Parafit [2] and HPCC [3] and the promiscuity is quantified using GES. Hence, we obtain a consensus promiscuity representation based on the comparison of 3D shapes and chemistry of ligands.Here, we show as an example the GES polypharmacology fingerprint calculated for ~800 targets linked to DrugBank [4] ligands. The performance of the approach is measured by comparing the present computational polypharmacology fingerprint with an in-house experimental polypharmacology fingerprint built using publically available experimental data for the ~800 targets that comprises the fingerprint. Matches between the computational and experimental polypharmacology fingerprints will be discussed.Detecting Drug Promiscuity using Gaussian Ensemble Screening. P�rez-Nueno, V.I.; Venkatraman, V.; Mavridis, L.; Ritchie, D.W. (2012) J. Chem. Inf. Model. 52,1948-1961.Protein docking using spherical polar Fourier correlations. Ritchie, D.W.; Kemp, G.J.L. (2000) Proteins 2, 178-194.Benchmarking of HPCC: A novel 3D molecular representation combining shape and pharmacophoric descriptors for efficient molecular similarity assessments. Karaboga, A.S.; Petronin, F.; Marchetti, G.; Souchet, M.; Maigret, B. (2013) J. Mol. Graph. Model. 41, 20-30.DrugBank: a knowledgebase for drugs,drug actions and drug targets. Wishart, D.S.; Knox, C.; Guo, A.C.; Cheng, D.; Shrivastava, S.; Tzur, D.; Gautam, B.; Hassanali, M. (2008) Nucleic Acids Res. (Database issue): D901-906.

GES polypharmacology fingerprints: A novel and powerful drug repositioning tool

246th National Meeting (2013)

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