We previously introduced a spherical harmonic (SH) approach to compare the 3D shapes of ligands and target binding pockets [1][2][3]. Here, we present a  novel extension of this approach to predict relationships between drug classes, which we call Gaussian Ensemble Screening (GUESS). This allows promiscuous ligands and targets to be predicted rapidly without requiring thousands of bootstrap comparisons as in current promiscuity prediction approaches [4].When using GUESS to find relationships between drug classes in a subset of the MDDR, our approach detects interesting relationships between targets such as GABA A and tyrosine-specific protein kinase, and ACE and neutral endopeptidase, for example, whose dual inhibitors have both been confirmed  experimentally [5][6]. Hence, GUESS is a useful way to study polypharmacology relationships, and could provide a novel approach for drug repositioning. Using spherical harmonic surface property      representations for ligand-based virtual screening. P�rez-Nueno, V. I.;      Venkatraman, V.; Mavridis, L.; Clark, T.; Ritchie, D.W. (2011) Molecular Informatics 30, 151-159.Using Consensus-Shape Clustering to      Identify Promiscuous Ligands and Protein targets and to Choose the Right      Query for Shape-Based Virtual Screening. P�rez-Nueno, V. I.; Ritchie, D.W.      (2011) J. Chem. Inf. Model. 51,      1233-1248.Predicting drug polypharmacology using a      novel surface property similarity-based approach. P�rez-Nueno, V. I.;      Venkatraman, V.; Mavridis, L.; Ritchie, D.W. (2011) Journal of Cheminformatics 3 (Suppl 1), O19.Predicting new      molecular targets for known drugs. Keiser, M. J. et al. (2009) Nature 462, 175-181.Regulation of GABAA receptor by protein      tyrosine kinases in frog pituitary melanotrophs. Castel H, Louiset E,      Anouar Y, Le Foll F, Cazin L, Vaudry H. (2000) J Neuroendocrinol. 12, 41-52.Dual ACE and Neutral Endopeptidase      Inhibitors: Novel Therapy for Patients with Cardiovascular Disorders.      Tabrizchi, Reza (2003) Drugs 63,      2185-2202.

Gaussian ensemble screening (GUESS): A new approach to polypharmacology and virtual screening

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.