title: Diverse, high-quality test set for the validation of protein-ligand docking performance.
abstract: A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered according to the protein sequences, and clusters have been discarded if they do not represent proteins thought to be of direct interest to the pharmaceutical or agrochemical industry. Rules have been used to exclude complexes containing non-drug-like ligands. One complex from each cluster has been selected where a structure of sufficient quality was available. The final Astex diverse set contains 85 diverse, relevant protein-ligand complexes, which have been prepared in a format suitable for docking and are to be made freely available to the entire research community (http://www.ccdc.cam.ac.uk). The performance of the docking program GOLD against the new set is assessed using a variety of protocols. Relatively unbiased protocols give success rates of approximately 80% for redocking into native structures, but it is possible to get success rates of over 90% with some protocols.
authors.affiliation: Astex Therapeutics, Ltd., 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hartshorn
authors.forename: Marcel L
authors.initials: ML
authors.lastname: Verdonk
authors.forename: Gianni
authors.initials: G
authors.lastname: Chessari
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Brewerton
authors.forename: Wijnand T M
authors.initials: WT
authors.lastname: Mooij
authors.forename: Paul N
authors.initials: PN
authors.lastname: Mortenson
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D020539:Sequence Analysis, Protein
chemical_list: D008024:Ligands; D011506:Proteins