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Validation of ligands in macromolecular structures determined by X-ray crystallography
- Source :
- Acta Crystallographica. Section D, Structural Biology, Acta Crystallographica Section D Structural Biology
- Publication Year :
- 2018
- Publisher :
- International Union of Crystallography, 2018.
-
Abstract
- Better metrics are required to be able to assess small-molecule ligands in macromolecular structures in Worldwide Protein Data Bank validation reports. The local ligand density fit (LLDF) score currently used to assess ligand electron-density fit outliers produces a substantial number of false positives and false negatives.<br />Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) play a crucial role in structure-guided drug discovery and design, and also provide atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. The quality with which small-molecule ligands have been modelled in Protein Data Bank (PDB) entries has been, and continues to be, a matter of concern for many investigators. Correctly interpreting whether electron density found in a binding site is compatible with the soaked or co-crystallized ligand or represents water or buffer molecules is often far from trivial. The Worldwide PDB validation report (VR) provides a mechanism to highlight any major issues concerning the quality of the data and the model at the time of deposition and annotation, so the depositors can fix issues, resulting in improved data quality. The ligand-validation methods used in the generation of the current VRs are described in detail, including an examination of the metrics to assess both geometry and electron-density fit. It is found that the LLDF score currently used to identify ligand electron-density fit outliers can give misleading results and that better ligand-validation metrics are required.
- Subjects :
- 0301 basic medicine
Models, Molecular
PDB
Computer science
Macromolecular Substances
Protein Conformation
Protein Data Bank (RCSB PDB)
Computational biology
Crystallography, X-Ray
03 medical and health sciences
Structural Biology
Protein Data Bank
Molecule
Humans
Binding site
Databases, Protein
validation
030102 biochemistry & molecular biology
Molecular Structure
Ligand
Drug discovery
ligands
nutritional and metabolic diseases
Proteins
computer.file_format
three-dimensional macromolecular structure
Research Papers
nervous system diseases
030104 developmental biology
Data quality
computer
Macromolecule
Subjects
Details
- Language :
- English
- ISSN :
- 20597983
- Volume :
- 74
- Issue :
- Pt 3
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica. Section D, Structural Biology
- Accession number :
- edsair.doi.dedup.....58dda2ee30ad569b6afecf528a877193