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 »
- Authors:
-
more »
- Univ. of California, Berkeley, CA (United States)
- DART NeuroScience, LLC, San Diego, CA (United States)
- Bruker AXS, Inc., Madison, WI (United States)
- Schrodinger, Inc., New York, NY (United States)
- Rutgers Univ., Piscataway, NJ (United States)
- National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States). Biosystems and Biomaterials Division
- Genentech, Inc., South San Francisco, CA (United States)
- National Library of Medicine (NLM), Bethesda, MD (United States). National Center for Biotechnology Information
- Global Phasing Ltd., Cambridge (United Kingdom)
- Univ. of Kent, Canterbury (United Kingdom); Charles River Ltd., Cambridge (United Kingdom)
- Rutgers Univ., Piscataway, NJ (United States); Univ. of California, San Diego, CA (United States)
- Novartis Institutes for BioMedical Research, Cambridge, MA (United States)
- OpenEye Scientific, Cambridge, MA (United States)
- MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
- Univ. of California, San Diego, CA (United States)
- Cambridge Crystallographic Data Centre, Cambridge (United Kingdom)
- Lilly Biotechnology Center, San Diego, CA (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Wellcome Genome Campus, Hinxton (United States)
- Univ. of Oxford (United Kingdom). Structural Genomics Consortium
- Univ. of Queensland, St Lucia, QLD (Australia)
- Univ. of Wisconsin, Madison, WI (United States)
- Univ. of Virginia, Charlottesville, VA (United States)
- MRC Laboratory of Molecular Biology, Cambridge (United Kingdom)
- Osaka Univ. (Japan). Protein Data Bank Japan
- National Inst. of Health (NIH), Bethesda, MD (United States).National Cancer Inst.
- GlaxoSmithKline, Collegeville, PA (United States)
- Agios Pharmaceuticals, Inc., Cambridge, MA
- Bristol-Myers Squibb Research and Development, Pennington, NJ (United States)
- Univ. of Cambridge (United Kingdom)
- Merck Research Lab., West Point, PA (United States)
- Janssen Pharmaceuticals, Inc., Spring House, PA (United States)
- Science For Solutions, LLC, West Windsor, NJ (United States)
- Masaryk University Brno (Czech Republic)
- Univ. of Toronto, ON (Canada)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Oregon State Univ., Corvallis, OR (United States)
- OpenEye Scientific, Cambridge, MA (united States)
- 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.
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
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.
@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}
}
Web of Science
Works referenced in this record:
Announcing the worldwide Protein Data Bank
journal, December 2003
- Berman, Helen; Henrick, Kim; Nakamura, Haruki
- Nature Structural & Molecular Biology, Vol. 10, Issue 12
Calculation of an OMIT map
journal, June 1988
- Bhat, T. N.
- Journal of Applied Crystallography, Vol. 21, Issue 3
OMITMAP: An electron density map suitable for the examination of errors in a macromolecular model
journal, August 1984
- Bhat, T. N.; Cohen, G. H.
- Journal of Applied Crystallography, Vol. 17, Issue 4
Retrieval of Crystallographically-Derived Molecular Geometry Information
journal, November 2004
- Bruno, Ian J.; Cole, Jason C.; Kessler, Magnus
- Journal of Chemical Information and Computer Sciences, Vol. 44, Issue 6
NORINE: a database of nonribosomal peptides
journal, December 2007
- Caboche, S.; Pupin, M.; Leclere, V.
- Nucleic Acids Research, Vol. 36, Issue Database
Specification of Molecular Chirality
journal, April 1966
- Cahn, R. S.; Ingold, Christopher; Prelog, V.
- Angewandte Chemie International Edition in English, Vol. 5, Issue 4
Limitations and lessons in the use of X-ray structural information in drug design
journal, October 2008
- Davis, A.; Stgallay, S.; Kleywegt, G.
- Drug Discovery Today, Vol. 13, Issue 19-20
Improving the representation of peptide-like inhibitor and antibiotic molecules in the Protein Data Bank: Representation of Peptide-Like Inhibitor and Antibiotic Molecules
journal, March 2014
- Dutta, Shuchismita; Dimitropoulos, Dimitris; Feng, Zukang
- Biopolymers, Vol. 101, Issue 6
Ligand Depot: a data warehouse for ligands bound to macromolecules
journal, April 2004
- Feng, Z.; Chen, L.; Maddula, H.
- Bioinformatics, Vol. 20, Issue 13
Automatic generation of 3D-atomic coordinates for organic molecules
journal, January 1990
- Gasteiger, J.; Rudolph, C.; Sadowski, J.
- Tetrahedron Computer Methodology, Vol. 3, Issue 6
Implementing an X-ray validation pipeline for the Protein Data Bank
journal, March 2012
- Gore, Swanand; Velankar, Sameer; Kleywegt, Gerard J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
The Cambridge Structural Database in Retrospect and Prospect
journal, January 2014
- Groom, Colin R.; Allen, Frank H.
- Angewandte Chemie International Edition, Vol. 53, Issue 3
Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database
journal, March 2010
- Hawkins, Paul C. D.; Skillman, A. Geoffrey; Warren, Gregory L.
- Journal of Chemical Information and Modeling, Vol. 50, Issue 4
Pyrrolidine Carboxamides as a Novel Class of Inhibitors of Enoyl Acyl Carrier Protein Reductase from Mycobacterium tuberculosis
journal, September 2006
- He, Xin; Alian, Akram; Stroud, Robert
- Journal of Medicinal Chemistry, Vol. 49, Issue 21
Works referencing / citing this record:
Structural biology data archiving - where we are and what lies ahead
journal, May 2018
- Kleywegt, Gerard J.; Velankar, Sameer; Patwardhan, Ardan
- FEBS Letters, Vol. 592, Issue 12
Getting the chemistry right: protonation, tautomers and the importance of H atoms in biological chemistry
journal, February 2017
- Bax, Ben; Chung, Chun-wa; Edge, Colin
- Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 2
ProteinsPlus: a web portal for structure analysis of macromolecules
text, January 2017
- Faehrrolfes, Rainer; Bietz, Stefan; Flachsenberg, Florian
- Charité - Universitätsmedizin Berlin
Introduction to crystallographic refinement of macromolecular atomic models
journal, July 2019
- Urzhumtsev, Alexandre G.; Lunin, Vladimir Y.
- Crystallography Reviews, Vol. 25, Issue 3
Analysis of the quality of crystallographic data and the limitations of structural models
journal, October 2017
- Arkhipova, Valentina; Guskov, Albert; Slotboom, Dirk-Jan
- The Journal of General Physiology, Vol. 149, Issue 12
Estimation of the protein–ligand interaction energy for model building and validation
journal, March 2017
- Beshnova, Daria A.; Pereira, Joana; Lamzin, Victor S.
- Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 3
Conformational energy range of ligands in protein crystal structures: The difficult quest for accurate understanding
journal, February 2017
- Peach, Megan L.; Cachau, Raul E.; Nicklaus, Marc C.
- Journal of Molecular Recognition, Vol. 30, Issue 8
Preclinical pharmacology of AZD9977: A novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion
journal, February 2018
- Bamberg, Krister; Johansson, Ulrika; Edman, Karl
- PLOS ONE, Vol. 13, Issue 2
Protein Data Bank: the single global archive for 3D macromolecular structure data
journal, October 2018
- Burley, Stephen K.; Berman, Helen M.; Bhikadiya, Charmi
- Nucleic Acids Research, Vol. 47, Issue D1
Crystallography and Databases
journal, August 2017
- Bruno, Ian; Gražulis, Saulius; Helliwell, John R.
- Data Science Journal, Vol. 16
ProteinsPlus: a web portal for structure analysis of macromolecules
journal, May 2017
- Fährrolfes, Rainer; Bietz, Stefan; Flachsenberg, Florian
- Nucleic Acids Research, Vol. 45, Issue W1
Estimation of the protein–ligand interaction energy for model building and validation
text, January 2017
- Beshnova, Daria A.; Pereira, Joana; Lamzin, Victor
- Deutsches Elektronen-Synchrotron, DESY, Hamburg