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

Abstract

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?more » 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.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [10];  [11];  [5];  [12];  [13];  [14];  [15];  [5];  [16];  [7];  [17] more »;  [4];  [18];  [19];  [20];  [5];  [21];  [22];  [5];  [23];  [5];  [24];  [25];  [25];  [13];  [26];  [27];  [28];  [27];  [29];  [30];  [5];  [29];  [19];  [31];  [32];  [33];  [34];  [35];  [36];  [37];  [19];  [16];  [38];  [5];  [39];  [5];  [5] « less
+ Show Author Affiliations
  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)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1260571
Alternate Identifier(s):
OSTI ID: 1379278
Report Number(s):
LA-UR-16-22772
Journal ID: ISSN 0969-2126; PII: S0969212616000769
Grant/Contract Number:  
DBI 1338415; 104948; GM109046; GM111528; AC52-06NA25396; AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 24; Journal Issue: 4; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ligand structure validation; ligand structure; drug target structure; cocrystal structure; protein-ligand complex; Protein Data Bank

Citation Formats

Adams, Paul  D., Aertgeerts, Kathleen, Bauer, Cary, Bell, Jeffrey A., Berman, Helen  M., Bhat, Talapady  N., Blaney, Jeff  M., Bolton, Evan, Bricogne, Gerard, Brown, David, Burley, Stephen  K., Case, David  A., Clark, Kirk  L., Darden, Tom, Emsley, Paul, Feher, Victoria  A., Feng, Zukang, Groom, Colin  R., Harris, Seth  F., Hendle, Jorg, Holder, Thomas, Joachimiak, Andrzej, Kleywegt, Gerard  J., Krojer, Tobias, Marcotrigiano, Joseph, Mark, Alan  E., Markley, John  L., Miller, Matthew, Minor, Wladek, Montelione, Gaetano  T., Murshudov, Garib, Nakagawa, Atsushi, Nakamura, Haruki, Nicholls, Anthony, Nicklaus, Marc, Nolte, Robert  T., Padyana, Anil  K., Peishoff, Catherine E., Pieniazek, Susan, Read, Randy  J., Shao, Chenghua, Sheriff, Steven, Smart, Oliver, Soisson, Stephen, Spurlino, John, Stouch, Terry, Svobodova, Radka, Tempel, Wolfram, Terwilliger, Thomas  C., Tronrud, Dale, Velankar, Sameer, Ward, Suzanna  C., Warren, Gregory  L., Westbrook, John  D., Williams, Pamela, Yang, Huanwang, and Young, Jasmine. Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop. United States: N. p., 2016. Web. doi:10.1016/j.str.2016.02.017.
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Adams, Paul  D., Aertgeerts, Kathleen, Bauer, Cary, Bell, Jeffrey A., Berman, Helen  M., Bhat, Talapady  N., Blaney, Jeff  M., Bolton, Evan, Bricogne, Gerard, Brown, David, Burley, Stephen  K., Case, David  A., Clark, Kirk  L., Darden, Tom, Emsley, Paul, Feher, Victoria  A., Feng, Zukang, Groom, Colin  R., Harris, Seth  F., Hendle, Jorg, Holder, Thomas, Joachimiak, Andrzej, Kleywegt, Gerard  J., Krojer, Tobias, Marcotrigiano, Joseph, Mark, Alan  E., Markley, John  L., Miller, Matthew, Minor, Wladek, Montelione, Gaetano  T., Murshudov, Garib, Nakagawa, Atsushi, Nakamura, Haruki, Nicholls, Anthony, Nicklaus, Marc, Nolte, Robert  T., Padyana, Anil  K., Peishoff, Catherine E., Pieniazek, Susan, Read, Randy  J., Shao, Chenghua, Sheriff, Steven, Smart, Oliver, Soisson, Stephen, Spurlino, John, Stouch, Terry, Svobodova, Radka, Tempel, Wolfram, Terwilliger, Thomas  C., Tronrud, Dale, Velankar, Sameer, Ward, Suzanna  C., Warren, Gregory  L., Westbrook, John  D., Williams, Pamela, Yang, Huanwang, & Young, Jasmine. Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop. United States. https://doi.org/10.1016/j.str.2016.02.017
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Adams, Paul  D., Aertgeerts, Kathleen, Bauer, Cary, Bell, Jeffrey A., Berman, Helen  M., Bhat, Talapady  N., Blaney, Jeff  M., Bolton, Evan, Bricogne, Gerard, Brown, David, Burley, Stephen  K., Case, David  A., Clark, Kirk  L., Darden, Tom, Emsley, Paul, Feher, Victoria  A., Feng, Zukang, Groom, Colin  R., Harris, Seth  F., Hendle, Jorg, Holder, Thomas, Joachimiak, Andrzej, Kleywegt, Gerard  J., Krojer, Tobias, Marcotrigiano, Joseph, Mark, Alan  E., Markley, John  L., Miller, Matthew, Minor, Wladek, Montelione, Gaetano  T., Murshudov, Garib, Nakagawa, Atsushi, Nakamura, Haruki, Nicholls, Anthony, Nicklaus, Marc, Nolte, Robert  T., Padyana, Anil  K., Peishoff, Catherine E., Pieniazek, Susan, Read, Randy  J., Shao, Chenghua, Sheriff, Steven, Smart, Oliver, Soisson, Stephen, Spurlino, John, Stouch, Terry, Svobodova, Radka, Tempel, Wolfram, Terwilliger, Thomas  C., Tronrud, Dale, Velankar, Sameer, Ward, Suzanna  C., Warren, Gregory  L., Westbrook, John  D., Williams, Pamela, Yang, Huanwang, and Young, Jasmine. Tue . "Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop". United States. https://doi.org/10.1016/j.str.2016.02.017. https://www.osti.gov/servlets/purl/1260571.
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@article{osti_1260571,
title = {Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop},
author = {Adams, Paul  D. and Aertgeerts, Kathleen and Bauer, Cary and Bell, Jeffrey A. and Berman, Helen  M. and Bhat, Talapady  N. and Blaney, Jeff  M. and Bolton, Evan and Bricogne, Gerard and Brown, David and Burley, Stephen  K. and Case, David  A. and Clark, Kirk  L. and Darden, Tom and Emsley, Paul and Feher, Victoria  A. and Feng, Zukang and Groom, Colin  R. and Harris, Seth  F. and Hendle, Jorg and Holder, Thomas and Joachimiak, Andrzej and Kleywegt, Gerard  J. and Krojer, Tobias and Marcotrigiano, Joseph and Mark, Alan  E. and Markley, John  L. and Miller, Matthew and Minor, Wladek and Montelione, Gaetano  T. and Murshudov, Garib and Nakagawa, Atsushi and Nakamura, Haruki and Nicholls, Anthony and Nicklaus, Marc and Nolte, Robert  T. and Padyana, Anil  K. and Peishoff, Catherine E. and Pieniazek, Susan and Read, Randy  J. and Shao, Chenghua and Sheriff, Steven and Smart, Oliver and Soisson, Stephen and Spurlino, John and Stouch, Terry and Svobodova, Radka and Tempel, Wolfram and Terwilliger, Thomas  C. and Tronrud, Dale and Velankar, Sameer and Ward, Suzanna  C. and Warren, Gregory  L. and Westbrook, John  D. and Williams, Pamela and Yang, Huanwang and Young, Jasmine},
abstractNote = {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.},
doi = {10.1016/j.str.2016.02.017},
journal = {Structure},
number = 4,
volume = 24,
place = {United States},
year = {2016},
month = {4}
}
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