Quality assessment for molecular models: Difference between revisions

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Models resulting from [[NMR Ensembles of Models|solution NMR experiments]] account for about 15% of those published in the [[Protein Data Bank]]. These 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. NMR models are more likely to contain major errors <ref>Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. Sander B. Nabuurs, Chris. A. E. M. Spronk, Geerten W. Vuister, and Gert Vriend. (2006). PLoS Computational Biology 2: [http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020009 Open Access Full Text] [http://proteinexplorer.org/favlit/nmr.htm Precis]. DOI: 10.1371/journal.pcbi.0020009</ref> than are crystallographic models that have good [[Resolution]] and [[Free R]] values.
Models resulting from [[NMR Ensembles of Models|solution NMR experiments]] account for about 15% of those published in the [[Protein Data Bank]]. These 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. NMR models are more likely to contain major errors <ref>Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. Sander B. Nabuurs, Chris. A. E. M. Spronk, Geerten W. Vuister, and Gert Vriend. (2006). PLoS Computational Biology 2: [http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020009 Open Access Full Text] [http://proteinexplorer.org/favlit/nmr.htm Precis]. DOI: 10.1371/journal.pcbi.0020009</ref> than are crystallographic models that have good [[Resolution]] and [[Free R]] values.
==Global vs. Local Quality==
The indicators discussed above, notably [[resolution]], [[R value]], and [[free R]], asses the global quality of the model. However, quality and uncertainty are not uniformly distributed throughout the model. Rather, there are regions of higher and lower uncertainty and quality. Perhaps the easiest way to visualize local variations in uncertainty is to color the model by [[temperature]]. As explained in the article on [[Temperature]], in a temperature-colored model, red atoms have the highest uncertainty in their positions in the model.
The MolProbity server offers 3D visualization of atomic clashes, with indication of the severity of each clash. The presence of severe clashes indicates greater uncertainty in that local region of the model.
The orientation of the sidechains of Asn, Gln, and His cannot be determined from the electron density in a crystallographic experiment, because of the similarity in electron densities of carbon vs. nitrogen. It is usually straightforward to determine the correct orientation by examining the local environment and optimising hydrogen bonding. Unfortunately, is is common for these determinations not to be made in published crystallographic models. Fortunately, MolProbity does these determinations automatically, and corrects the model by flipping the sidechains of Asn, Gln and HIs when this is warranted.


==Further Reading==
==Further Reading==

Revision as of 00:19, 13 December 2009

Crystallographic ModelsCrystallographic Models

About 85% of the molecular models published in the Protein Data Bank come from X-ray crystallography experiments. These crystallographic models 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 ModelsNMR Models

Models resulting from solution NMR experiments account for about 15% of those published in the Protein Data Bank. These 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. NMR models are more likely to contain major errors [6] than are crystallographic models that have good Resolution and Free R values.

Global vs. Local QualityGlobal vs. Local Quality

The indicators discussed above, notably resolution, R value, and free R, asses the global quality of the model. However, quality and uncertainty are not uniformly distributed throughout the model. Rather, there are regions of higher and lower uncertainty and quality. Perhaps the easiest way to visualize local variations in uncertainty is to color the model by temperature. As explained in the article on Temperature, in a temperature-colored model, red atoms have the highest uncertainty in their positions in the model.

The MolProbity server offers 3D visualization of atomic clashes, with indication of the severity of each clash. The presence of severe clashes indicates greater uncertainty in that local region of the model.

The orientation of the sidechains of Asn, Gln, and His cannot be determined from the electron density in a crystallographic experiment, because of the similarity in electron densities of carbon vs. nitrogen. It is usually straightforward to determine the correct orientation by examining the local environment and optimising hydrogen bonding. Unfortunately, is is common for these determinations not to be made in published crystallographic models. Fortunately, MolProbity does these determinations automatically, and corrects the model by flipping the sidechains of Asn, Gln and HIs when this is warranted.

Further ReadingFurther Reading

Laskowski[7] has provided an outstandingly clear and succinct overview of how to assess model quality. See also the 2007 overview by Kleywegt[8] For examples of published crystallographic errors, see Laskowski, and Kleywegt, 2000[9], and Kleywegt and Brünger, 1996[10]. Kleywegt has also provided an excellent on-line tutorial on model validation[11].

See AlsoSee Also

Content DonorsContent Donors

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

  1. ↑ 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].
  2. ↑ PDBREPORT Database
  3. ↑ 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.
  4. ↑ MolProbity Server: All-atom contact analysis, flip corrections for Asn, Gln, His, clash analysis, Ramachandran analysis, and more.
  5. ↑ Brown EN, Ramaswamy S. 2007. Quality of protein crystal structures. Biol. Crystallography 63:941-950.
  6. ↑ Traditional biomolecular structure determination by NMR spectroscopy allows for major errors. Sander B. Nabuurs, Chris. A. E. M. Spronk, Geerten W. Vuister, and Gert Vriend. (2006). PLoS Computational Biology 2: Open Access Full Text Precis. DOI: 10.1371/journal.pcbi.0020009
  7. ↑ 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.
  8. ↑ Kleywegt, GJ. 2007. Quality control and validation. Methods Mol. Biol. 364:255-72. PubMed.
  9. ↑ Kleywegt, GJ. 2000. Validation of protein crystal structures. Acta. Crystallogr. D. Biol. Crystallogr. 56:249-265
  10. ↑ Kleywegt, GJ, AT Brünger. 1996. Checking your imagination: applications of the free R value. Structure 4:897-904. PubMed.
  11. ↑ Practical Model Validation by Gerard Kleywegt, University of Uppsala, Sweden

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