Quality assessment for molecular models
The molecular models published in the Protein Data Bank for X-ray crystallography vary widely in quality, and rarely they are grossly incorrect[1]. Generally, model quality is indicated by the resolution of the model, the R value, and especially the Free R. Useful information on model quality, including the Ramachandran plots, can be obtained from PDBReports[2]. All-atom contact analysis[3] is a powerful newer method for finding and correcting errors in crystallographic models, made easy and convenient with the MolProbity Server[4].
Generally, crystallographic models are reliable in most details when they have resolutions of 2.0 Å or better (the lower the number the better), R values of 0.20 or less, and Free R values of 0.25 or less. However, new and important structural insights are often provided by models with much lower resolution. Interestingly, the quality of published molecular models is inversely related to the impacts of the journals in which they are published[5].
NMR models are generally less reliable than crystallographic models because the method yields less detailed information. For NMR, there are no widely reported global error estimates equivalent to the crystallographic R value and Free R. Unlike with crystallographic results, it is not possible to distinguish reliable from unreliable NMR models from information included in the PDB files.
Laskowski[6] has provided an outstandingly clear and succinct overview of how to assess model quality. See also the 2007 overview by Kleywegt[7] For examples of published crystallographic errors, see Laskowski, and Kleywegt, 2000[8], and Kleywegt and Brünger, 1996[9]. Kleywegt has also provided an excellent on-line tutorial on model validation[10].
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Portions of this page were adapted from the Glossary of ProteinExplorer.Org, with the permission of the principal author, Eric Martz.
References and WebsitesReferences and Websites
- ↑ Miller, Greg (2007) A Scientist's Nightmare: Software Problem Leads to Five Retractions. [http://www.sciencemag.org/cgi/content/summary/314/5807/1856 Science 22 December 2006: 314:1856-7. DOI: 10.1126/science.314.5807.1856].
- ↑ PDBREPORT Database
- ↑ Richardson, Jane S. (2003). All-atom contacts: a new approach to structure validation. Precis. Chapter 15 in Structural Bioinformatics (2003) edited by Philip E. Bourne and Helge Weissig, Wiley-Liss, 649 pages. Complete contents at structuralbioinformaticsbook.com.
- ↑ MolProbity Server: All-atom contact analysis, flip corrections for Asn, Gln, His, clash analysis, Ramachandran analysis, and more.
- ↑ Brown EN, Ramaswamy S. 2007. Quality of protein crystal structures. Biol. Crystallography 63:941-950.
- ↑ Laskowski, Roman A. 2003. Structural quality assurance. Chapter 14 in Structural Bioinformatics (2003) edited by Philip E. Bourne and Helge Weissig, Wiley-Liss, 649 pages. Complete contents at structuralbioinformaticsbook.com.
- ↑ Kleywegt, GJ. 2007. Quality control and validation. Methods Mol. Biol. 364:255-72. PubMed.
- ↑ Kleywegt, GJ. 2000. Validation of protein crystal structures. Acta. Crystallogr. D. Biol. Crystallogr. 56:249-265
- ↑ Kleywegt, GJ, AT Brünger. 1996. Checking your imagination: applications of the free R value. Structure 4:897-904. PubMed.
- ↑ Practical Model Validation by Gerard Kleywegt, University of Uppsala, Sweden