A test of enhancing model accuracy in high-throughput crystallography

  • W. Bryan ArendallIII
  • Wolfram Tempel
  • Jane S. Richardson
  • Weihong Zhou
  • Shuren Wang
  • Ian W. Davis
  • Zhi-Jie Liu
  • John P. Rose
  • W. Michael Carson
  • Ming Luo
  • David C. RichardsonEmail author
  • Bi-Cheng Wang


The high throughput of structure determination pipelines relies on increased automation and, consequently, a reduction of time spent on interactive quality control. In order to meet and exceed current standards in model accuracy, new approaches are needed for the facile identification and correction of model errors during refinement. One such approach is provided by the validation and structure-improvement tools of the MOLPROBITY web service. To test their effectiveness in high-throughput mode, a large subset of the crystal structures from the SouthEast Collaboratory for Structural Genomics (SECSG) has used protocols based on the MOLPROBITY tools. Comparison of 29 working-set and 19 control-set SECSG structures shows that working-set outlier scores for updated Ramachandran-plot, sidechain rotamer, and all-atom steric criteria have been improved by factors of 5- to 10-fold (relative to the control set or to a Protein Data Bank sample), while quality of covalent geometry, Rwork, Rfree, electron density and difference density are maintained or improved. Some parts of this correction process are already fully automated; other parts involve manual rebuilding of conformations flagged by the tests as trapped in the wrong local minimum, often altering features of functional significance. The ease and effectiveness of this technique shows that macromolecular crystal structures from either traditional or high-throughput determinations can feasibly reach a new level of excellence in conformational accuracy and reliability.


all-atom contacts MOLPROBITY Ramachandran plot sidechain rotamers structural genomics structure validation 


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Copyright information

© Springer 2005

Authors and Affiliations

  • W. Bryan ArendallIII
    • 1
  • Wolfram Tempel
    • 2
  • Jane S. Richardson
    • 1
  • Weihong Zhou
    • 2
  • Shuren Wang
    • 1
    • 4
  • Ian W. Davis
    • 1
  • Zhi-Jie Liu
    • 2
  • John P. Rose
    • 2
  • W. Michael Carson
    • 3
  • Ming Luo
    • 3
  • David C. Richardson
    • 1
    Email author
  • Bi-Cheng Wang
    • 2
  1. 1.Department of BiochemistryDuke University Medical CenterDurhamUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of GeorgiaAthensUSA
  3. 3.Center for Biophysical Sciences and EngineeringUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of Molecular Physiology and Biological PhysicsUniversity of VirginiaCharlottesvilleUSA

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