title: Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules.
abstract: The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have systematically revised all torsion rules to better identify highly strained conformations and minimize the number of false alerts for CSD small molecule X-ray structures. For this new release, we added or substantially modified 78 torsion patterns and reviewed all angles and tolerance intervals. The overall number of red alerts for a filtered CSD data set with 130 000 structures was reduced by a factor of 4 compared to the predecessor. This is of clear advantage in 3D virtual screening where hits should only be removed by a conformational filter if they are in energetically inaccessible conformations.
authors.affiliation: Molecular Design and Chemical Biology, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd , Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guba
authors.affiliation: Center for Bioinformatics, University of Hamburg , Bundesstrasse 43, D-20146 Hamburg, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Meyder
authors.affiliation: Center for Bioinformatics, University of Hamburg , Bundesstrasse 43, D-20146 Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rarey
authors.affiliation: Molecular Design and Chemical Biology, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd , Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hert
mesh_terms: D019295:Computational Biology / Q000379:methods*; D062313:Databases, Pharmaceutical; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D054852:Small Molecule Libraries