title: Interactive and Versatile Navigation of Structural Databases.
abstract: We present CSD-CrossMiner, a novel tool for pharmacophore-based searches in crystal structure databases. Intuitive pharmacophore queries describing, among others, protein-ligand interaction patterns, ligand scaffolds, or protein environments can be built and modified interactively. Matching crystal structures are overlaid onto the query and visualized as soon as they are available, enabling the researcher to quickly modify a hypothesis on the fly. We exemplify the utility of the approach by showing applications relevant to real-world drug discovery projects, including the identification of novel fragments for a specific protein environment or scaffold hopping. The ability to concurrently search protein-ligand binding sites extracted from the Protein Data Bank (PDB) and small organic molecules from the Cambridge Structural Database (CSD) using the same pharmacophore query further emphasizes the flexibility of CSD-CrossMiner. We believe that CSD-CrossMiner closes an important gap in mining structural data and will allow users to extract more value from the growing number of available crystal structures.
authors.affiliation: Cambridge Crystallographic Data Centre , 12 Union Road, Cambridge CB2 1EZ, U.K.
authors.forename: Oliver
authors.initials: O
authors.lastname: Korb
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hert
authors.affiliation: Desert Scientific Software Pty Ltd. , Level 5 Nexus Building, Norwest Business Park, 4 Columbia Court, Baulkham Hills, NSW 2153, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Taylor
authors.affiliation: Cambridge Crystallographic Data Centre , 12 Union Road, Cambridge CB2 1EZ, U.K.
authors.forename: Jason
authors.initials: J
authors.lastname: Cole
authors.affiliation: Cambridge Crystallographic Data Centre , 12 Union Road, Cambridge CB2 1EZ, U.K.
authors.forename: Colin
authors.initials: C
authors.lastname: Groom
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Stahl
mesh_terms: D018360:Crystallography, X-Ray; D030562:Databases, Protein; D055808:Drug Discovery; D008024:Ligands; D011506:Proteins / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins