naa a22 4500 528787039 20180924065502.0 cr unu---uuuuu 180924e20110727xx s 000 0 eng 10.3929/ethz-b-000038574 doi 10.1371/journal.pone.0021554 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/38574 Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors [Elektronische Daten] [Gisbert Schneider, Quan Wang, Kerstin Birod, Carlo Angioni, Sabine Grösch, Tim Geppert, Petra Schneider, Matthias Rupp] PLoS ONE Open access ethresearch Background Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Schneider Gisbert joint author Wang Quan joint author Birod Kerstin joint author Angioni Carlo joint author Grösch Sabine joint author Geppert Tim joint author Schneider Petra joint author Rupp Matthias joint author PLoS ONE Lawrence, KS, USA : Public Library of Science 6 (7), p. e21554 1932-6203 http://hdl.handle.net/20.500.11850/38574 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/38574 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Schneider Gisbert joint author ETHRESEARCH 700 1- Wang Quan joint author ETHRESEARCH 700 1- Birod Kerstin joint author ETHRESEARCH 700 1- Angioni Carlo joint author ETHRESEARCH 700 1- Grösch Sabine joint author ETHRESEARCH 700 1- Geppert Tim joint author ETHRESEARCH 700 1- Schneider Petra joint author ETHRESEARCH 700 1- Rupp Matthias joint author ETHRESEARCH 773 0- PLoS ONE Lawrence, KS, USA : Public Library of Science 6 (7), p. e21554 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access