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Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors

Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors

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WANG, Quan, Kerstin BIROD, Carlo ANGIONI, Sabine GRÖSCH, Tim GEPPERT, Petra SCHNEIDER, Matthias RUPP, Gisbert SCHNEIDER, 2011. Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors. In: PLoS one. Public Library of Science (PLoS). 6(7), e21554. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0021554

@article{Wang2011Spher-52730, title={Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors}, year={2011}, doi={10.1371/journal.pone.0021554}, number={7}, volume={6}, journal={PLoS one}, author={Wang, Quan and Birod, Kerstin and Angioni, Carlo and Grösch, Sabine and Geppert, Tim and Schneider, Petra and Rupp, Matthias and Schneider, Gisbert}, note={Article Number: e21554} }

Birod, Kerstin Schneider, Gisbert Background:<br />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.<br /><br />Methodology/Principal Findings:<br />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.<br /><br />Conclusions/Significance:<br />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. Wang, Quan Schneider, Gisbert Rupp, Matthias Schneider, Petra Grösch, Sabine Wang, Quan Attribution 4.0 International Rupp, Matthias Angioni, Carlo Schneider, Petra Grösch, Sabine 2011 2021-02-05T08:22:27Z Angioni, Carlo Geppert, Tim 2021-02-05T08:22:27Z Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors Geppert, Tim Birod, Kerstin eng

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