Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors
| LEADER | naa a22 4500 | ||
|---|---|---|---|
| 001 | 528787039 | ||
| 005 | 20180924065502.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924e20110727xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000038574 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0021554 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/38574 | ||
| 245 | 0 | 0 | |a Spherical Harmonics Coefficients for Ligand-Based Virtual Screening of Cyclooxygenase Inhibitors |h [Elektronische Daten] |c [Gisbert Schneider, Quan Wang, Kerstin Birod, Carlo Angioni, Sabine Grösch, Tim Geppert, Petra Schneider, Matthias Rupp] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Schneider |D Gisbert |e joint author | |
| 700 | 1 | |a Wang |D Quan |e joint author | |
| 700 | 1 | |a Birod |D Kerstin |e joint author | |
| 700 | 1 | |a Angioni |D Carlo |e joint author | |
| 700 | 1 | |a Grösch |D Sabine |e joint author | |
| 700 | 1 | |a Geppert |D Tim |e joint author | |
| 700 | 1 | |a Schneider |D Petra |e joint author | |
| 700 | 1 | |a Rupp |D Matthias |e joint author | |
| 773 | 0 | |t PLoS ONE |d Lawrence, KS, USA : Public Library of Science |g 6 (7), p. e21554 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/38574 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/38574 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schneider |D Gisbert |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Wang |D Quan |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Birod |D Kerstin |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Angioni |D Carlo |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Grösch |D Sabine |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Geppert |D Tim |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schneider |D Petra |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Rupp |D Matthias |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d Lawrence, KS, USA : Public Library of Science |g 6 (7), p. e21554 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||