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Title: Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop

Journal Article · · Structure
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  1. Univ. of California, Berkeley, CA (United States)
  2. DART NeuroScience, LLC, San Diego, CA (United States)
  3. Bruker AXS, Inc., Madison, WI (United States)
  4. Schrodinger, Inc., New York, NY (United States)
  5. Rutgers Univ., Piscataway, NJ (United States)
  6. National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States). Biosystems and Biomaterials Division
  7. Genentech, Inc., South San Francisco, CA (United States)
  8. National Library of Medicine (NLM), Bethesda, MD (United States). National Center for Biotechnology Information
  9. Global Phasing Ltd., Cambridge (United Kingdom)
  10. Univ. of Kent, Canterbury (United Kingdom); Charles River Ltd., Cambridge (United Kingdom)
  11. Rutgers Univ., Piscataway, NJ (United States); Univ. of California, San Diego, CA (United States)
  12. Novartis Institutes for BioMedical Research, Cambridge, MA (United States)
  13. OpenEye Scientific, Cambridge, MA (United States)
  14. MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
  15. Univ. of California, San Diego, CA (United States)
  16. Cambridge Crystallographic Data Centre, Cambridge (United Kingdom)
  17. Lilly Biotechnology Center, San Diego, CA (United States)
  18. Argonne National Lab. (ANL), Argonne, IL (United States)
  19. Wellcome Genome Campus, Hinxton (United States)
  20. Univ. of Oxford (United Kingdom). Structural Genomics Consortium
  21. Univ. of Queensland, St Lucia, QLD (Australia)
  22. Univ. of Wisconsin, Madison, WI (United States)
  23. Univ. of Virginia, Charlottesville, VA (United States)
  24. MRC Laboratory of Molecular Biology, Cambridge (United Kingdom)
  25. Osaka Univ. (Japan). Protein Data Bank Japan
  26. National Inst. of Health (NIH), Bethesda, MD (United States).National Cancer Inst.
  27. GlaxoSmithKline, Collegeville, PA (United States)
  28. Agios Pharmaceuticals, Inc., Cambridge, MA
  29. Bristol-Myers Squibb Research and Development, Pennington, NJ (United States)
  30. Univ. of Cambridge (United Kingdom)
  31. Merck Research Lab., West Point, PA (United States)
  32. Janssen Pharmaceuticals, Inc., Spring House, PA (United States)
  33. Science For Solutions, LLC, West Windsor, NJ (United States)
  34. Masaryk University Brno (Czech Republic)
  35. Univ. of Toronto, ON (Canada)
  36. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  37. Oregon State Univ., Corvallis, OR (United States)
  38. OpenEye Scientific, Cambridge, MA (united States)
  39. Astex Pharmaceuticals, Cambridge (United States)
+ Show Author Affiliations

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the PDB? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH)
Grant/Contract Number:
DBI 1338415; 104948; GM109046; GM111528; AC52-06NA25396; AC02-05CH11231
OSTI ID:
1260571
Alternate ID(s):
OSTI ID: 1379278
Report Number(s):
LA-UR-16-22772; PII: S0969212616000769
Journal Information:
Structure, Vol. 24, Issue 4; ISSN 0969-2126
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 51 works
Citation information provided by
Web of Science

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Cited By (15)

Structural biology data archiving - where we are and what lies ahead journal May 2018
ProteinsPlus: a web portal for structure analysis of macromolecules text January 2017
Analysis of the quality of crystallographic data and the limitations of structural models journal October 2017
Estimation of the protein–ligand interaction energy for model building and validation journal March 2017
Strategies for carbohydrate model building, refinement and validation journal February 2017
Conformational energy range of ligands in protein crystal structures: The difficult quest for accurate understanding journal February 2017
Preclinical pharmacology of AZD9977: A novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion journal February 2018
Validation of ligands in macromolecular structures determined by X-ray crystallography journal March 2018
Protein Data Bank: the single global archive for 3D macromolecular structure data journal October 2018
Crystallography and Databases journal August 2017
ProteinsPlus: a web portal for structure analysis of macromolecules journal May 2017
Estimation of the protein–ligand interaction energy for model building and validation text January 2017
The archiving and dissemination of biological structure data journal October 2016
Validation of Structures in the Protein Data Bank journal December 2017
The elusive ligand complexes of the DWARF14 strigolactone receptor journal January 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ligand structure validation
ligand structure
drug target structure
cocrystal structure
protein-ligand complex
Protein Data Bank