title: Structural artifacts in protein-ligand X-ray structures: implications for the development of docking scoring functions.
abstract: The development of docking scoring functions requires high-resolution 3D structures of protein-ligand complexes for which the binding affinity of the ligand has been measured experimentally. Protein-ligand binding affinities are measured in solution experiments, and high resolution protein-ligand structures can be determined only by X-ray crystallography. Protein-ligand scoring functions must therefore reproduce solution binding energies using analyses of proteins in a crystal environment. We present an analysis of the prevalence of crystal-induced artifacts and water-mediated contacts in protein-ligand complexes and demonstrate the effect that these can have on the performance of protein-ligand scoring functions. We find 36% of ligands in the PDBBind 2007 refined data set to be influenced by crystal contacts and find the performance of a scoring function to be affected by these. A Web server for detecting crystal contacts in protein-ligand complexes is available at http://enzyme.ucd.ie/LIGCRYST .
authors.affiliation: School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Chresten R
authors.initials: CR
authors.lastname: Søndergaard
authors.forename: Alison Elizabeth
authors.initials: AE
authors.lastname: Garrett
authors.forename: Tommy
authors.initials: T
authors.lastname: Carstensen
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pollastri
authors.forename: Jens Erik
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D016477:Artifacts; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D020407:Internet; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D014867:Water