Scientific Collaborators
The crystallography lab in Uppsala has a long tradition in the area of structure quality and validation. Alwyn Jones used Ramachandran plots in the mid-1980s to reject a few high-resolution structures from the database that was to be used in the crystallographic model-building program "O" for the construction and validation of new protein models.In 1990, Jones and Branden wrote a commentary in Nature addressing the fact that a number of high-profile structures, published in equally high- profile journals in the late 1980s, had turned out to be disastrously wrong. This seminal paper stimulated new developments in many labs to produce methods and tools that could be used to assess the quality (or lack thereof) of protein models.
In 1992, Gerard Kleywegt arrived in Uppsala, and he took an avid interest in matters of validation as well as "good crystallographic model-building practice". Together, Jones and Kleywegt have published a number of papers describing validation tools, suggesting improved practices, arguing for compulsary deposition of experimental data, and commenting on less desirable practices in the community of protein crystallographers. Kleywegt also wrote an extensive review article about validation and produced a web- based tutorial that is used in many courses.
As the PDB expanded, more and more non-experts began to use protein structures in their work, and the world-wide web became more advanced as well as omnipresent, work on providing easy access to the primary result of crystallographic experiments (namely, electron-density maps) began in Uppsala in the late 1990s. The result was EDS, the Uppsala Electron-Density Server, which provides access to maps, reflection files, and various plots and statistics for all crystal structures in the PDB for which experimental data has been deposited (~90% in recent years) and for which the published R-value can be reproduced to within five percentage points (~90% of the entries with experimental data, i.e., ~80% of all crystal structures in the PDB).
Publications
- Experimental data for structure papers.
- ValLigURL: a server for ligand-structure comparison and validation (pdf 328K)
Other References
- AM Davis, SJ Teague & GJ Kleywegt, "Applications and limitations of X-ray crystallographic data in structure-based ligand and drug design", Angewandte Chemie International Edition, 42, 2718-2736 (2003).
- GJ Kleywegt, "Crystallographic refinement of ligand complexes", Acta Crystallographica, D63, 94-100 (2007).
- GJ Kleywegt & H Hansson, "Retrieval and validation of structural information", In "Structural Genomics and High Throughput Structural Biology" (M Sundstrom, M Norin, A Edwards, Eds.), Taylor & Francis, Boca Raton, Chapter 10, pp. 185-222 (2005).
- GJ Kleywegt, K Henrick, EJ Dodson & DMF van Aalten, "Pound-wise but penny-foolish: How well do micromolecules fare in macromolecular refinement ?", Structure, 11, 1051-1059 (2003).
- G J Kleywegt & T A Jones, "Homo Crystallographicus - Quo Vadis?", Structure, 10, 465-472 (2002).
- G J Kleywegt, "Validation of protein crystal structures" (Topical review), Acta Crystallographica, D56, 249-265 (2000).
