title: Twilight reloaded: the peptide experience.
abstract: The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallographic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein-peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided.
authors.affiliation: k.k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084, USA.
authors.forename: Christian X
authors.initials: CX
authors.lastname: Weichenberger
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Pozharski
authors.affiliation: k.k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084, USA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rupp
mesh_terms: D000465:Algorithms; D000818:Animals; D018360:Crystallography, X-Ray; D057225:Data Mining; D030562:Databases, Protein; D004583:Electrons; D006801:Humans; D008024:Ligands; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D010455:Peptides; D011506:Proteins; D054852:Small Molecule Libraries; D019950:Mitogen-Activated Protein Kinase 1; D054467:Phospholipases A2; D057057:Serine Proteases
keywords: OMIT difference density; evidence-based reasoning; protein–peptide ligand structures; validation