title: The use of small-molecule structures to complement protein-ligand crystal structures in drug discovery.
abstract: Many ligand-discovery stories tell of the use of structures of protein-ligand complexes, but the contribution of structural chemistry is such a core part of finding and improving ligands that it is often overlooked. More than 800 000 crystal structures are available to the community through the Cambridge Structural Database (CSD). Individually, these structures can be of tremendous value and the collection of crystal structures is even more helpful. This article provides examples of how small-molecule crystal structures have been used to complement those of protein-ligand complexes to address challenges ranging from affinity, selectivity and bioavailability though to solubility.
authors.affiliation: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Groom
authors.affiliation: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Cole
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D062126:Databases, Chemical; D030562:Databases, Protein; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries
keywords: Cambridge Structural Database; conformation; interactions; small molecules; solubility