title: Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures.
abstract: As a result of substantial instrumental automation and the continuing improvement of software, crystallographic studies of biomolecules are conducted by non-experts in increasing numbers. While improved validation almost ensures that major mistakes in the protein part of structure models are exceedingly rare, in ligand-protein complex structures, which in general are most interesting to the scientist, ambiguous ligand electron density is often difficult to interpret and the modelled ligands are generally more difficult to properly validate. Here, (i) the primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) the most common categories of building errors or overinterpretation are classified; (iii) a few instructive and specific examples are discussed in detail, including an electron-density-based analysis of ligand structures that do not contain any ligands; (iv) means of avoiding such mistakes are suggested and the implications for database validity are discussed and (v) a user-friendly software tool that allows non-expert users to conveniently inspect ligand density is provided.
authors: Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA. epozh001@umaryland.edu
authors: Edwin
authors: E
authors: Pozharski
authors: Christian X
authors: CX
authors: Weichenberger
authors: Bernhard
authors: B
authors: Rupp
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray / Q000295:instrumentation / Q000379:methods / Q000592:standards; D030562:Databases, Protein; D004583:Electrons; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000592:standards; D015203:Reproducibility of Results
chemical_list: D008024:Ligands; D011506:Proteins
keywords: evidence-based reasoning; omit difference density; protein–ligand structures; validation