Avoidable errors in deposited macromolecular structures: an impediment to efficient data mining
Open Access
- 14 April 2014
- journal article
- research article
- Published by International Union of Crystallography (IUCr) in IUCrJ
- Vol. 1 (3), 179-193
- https://doi.org/10.1107/s2052252514005442
Abstract
Whereas the vast majority of the more than 85 000 crystal structures of macromolecules currently deposited in the Protein Data Bank are of high quality, some suffer from a variety of imperfections. Although this fact has been pointed out in the past, it is still worth periodic updates so that the metadata obtained by global analysis of the available crystal structures, as well as the utilization of the individual structures for tasks such as drug design, should be based on only the most reliable data. Here, selected abnormal deposited structures have been analysed based on the Bayesian reasoning that the correctness of a model must be judged against both the primary evidence as well as prior knowledge. These structures, as well as information gained from the corresponding publications (if available), have emphasized some of the most prevalent types of common problems. The errors are often perfect illustrations of the nature of human cognition, which is frequently influenced by preconceptions that may lead to fanciful results in the absence of proper validation. Common errors can be traced to negligence and a lack of rigorous verification of the models against electron density, creation of non-parsimonious models, generation of improbable numbers, application of incorrect symmetry, illogical presentation of the results, or violation of the rules of chemistry and physics. Paying more attention to such problems, not only in the final validation stages but during the structure-determination process as well, is necessary not only in order to maintain the highest possible quality of the structural repositories and databases but most of all to provide a solid basis for subsequent studies, including large-scale data-mining projects. For many scientists PDB deposition is a rather infrequent event, so the need for proper training and supervision is emphasized, as well as the need for constant alertness of reason and critical judgment as absolutely necessary safeguarding measures against such problems. Ways of identifying more problematic structures are suggested so that their users may be properly alerted to their possible shortcomings.Keywords
Funding Information
- National Institutes of Health (GM094662, GM093342, GM053163, GM094585)
- European Commission (PIIF-GA-2011-300025)
This publication has 78 references indexed in Scilit:
- Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamilyProceedings of the National Academy of Sciences of the United States of America, 2013
- Out-of-register β-sheets suggest a pathway to toxic amyloid aggregatesProceedings of the National Academy of Sciences of the United States of America, 2012
- Outcome of the First Electron Microscopy Validation Task Force MeetingStructure, 2012
- A New Generation of Crystallographic Validation Tools for the Protein Data BankStructure, 2011
- Structural and Functional Characterization of a Highly Specific Serpin in the Insect Innate ImmunityPublished by Elsevier BV ,2011
- Unmet challenges of structural genomicsCurrent Opinion in Structural Biology, 2010
- Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradationNature Structural & Molecular Biology, 2010
- Electron Spin-Echo Envelope Modulation (ESEEM) Reveals Water and Phosphate Interactions with the KcsA Potassium Channel,Biochemistry, 2010
- Inference of Macromolecular Assemblies from Crystalline StateJournal of Molecular Biology, 2007
- Between objectivity and subjectivityNature, 1990