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

Paul D Adams¹, Kathleen Aertgeerts², Cary Bauer³, Jeffrey A Bell⁴, Helen M Berman⁵, Talapady N Bhat⁶, Jeff M Blaney⁷, Evan Bolton⁸, Gerard Bricogne⁹, David Brown¹⁰, Stephen K Burley¹¹, David A Case¹², Kirk L Clark¹³, Tom Darden¹⁴, Paul Emsley¹⁵, Victoria A Feher¹⁶, Zukang Feng⁵, Colin R Groom¹⁷, Seth F Harris⁷, Jorg Hendle¹⁸, Thomas Holder⁴, Andrzej Joachimiak¹⁹, Gerard J Kleywegt²⁰, Tobias Krojer²¹, Joseph Marcotrigiano²², Alan E Mark²³, John L Markley²⁴, Matthew Miller²⁵, Wladek Minor²⁶, Gaetano T Montelione²⁷, Garib Murshudov¹⁵, Atsushi Nakagawa²⁸, Haruki Nakamura²⁸, Anthony Nicholls¹⁴, Marc Nicklaus²⁹, Robert T Nolte³⁰, Anil K Padyana³¹, Catherine E Peishoff³⁰, Susan Pieniazek³², Randy J Read³³, Chenghua Shao³⁴, Steven Sheriff³⁵, Oliver Smart²⁰, Stephen Soisson³⁶, John Spurlino³⁷, Terry Stouch³⁸, Radka Svobodova³⁹, Wolfram Tempel⁴⁰, Thomas C Terwilliger⁴¹, Dale Tronrud⁴², Sameer Velankar²⁰, Suzanna C Ward⁴³, Gregory L Warren¹⁴, John D Westbrook⁵, Pamela Williams⁴⁴, Huanwang Yang⁵, Jasmine Young⁵

Affiliations

¹ Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley Laboratory, Department of Bioengineering, UC Berkeley, Berkeley, CA 94720-8235, USA.
² DART NeuroScience, LLC, San Diego, CA 92131, USA.
³ Bruker AXS, Inc., Madison, WI 53711, USA.
⁴ Schrödinger, Inc., New York, NY 10036, USA.
⁵ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁶ Biosystems and Biomaterials Division, NIST, Gaithersburg, MD 20899, USA.
⁷ Genentech, Inc., South San Francisco, CA 94080, USA.
⁸ National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, MD 20894, USA.
⁹ Global Phasing Ltd., Cambridge CB3 0AX, UK.
¹⁰ School of Biosciences, University of Kent, Canterbury CT2 7NH, UK; Charles River Ltd., Structural Biology and Biophysics, Cambridge CB10 1XL, UK.
¹¹ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences and San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: stephen.burley@rcsb.org.
¹² Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
¹³ Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
¹⁴ OpenEye Scientific, Cambridge, MA 02142, USA.
¹⁵ MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
¹⁶ Drug Design Data Resource and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: vfeher@ucsd.edu.
¹⁷ Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK. Electronic address: groom@ccdc.cam.ac.uk.
¹⁸ Structural Biology, Lilly Biotechnology Center, San Diego, CA 92121, USA.
¹⁹ Structural Biology Center, Biosciences, Argonne National Laboratory, Argonne, IL 60439, USA.
²⁰ Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
²¹ Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
²² Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²³ School of Chemistry & Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia.
²⁴ BioMagResBank, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, USA.
²⁵ Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²⁶ Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
²⁷ Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²⁸ Protein Data Bank Japan, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
²⁹ Computer-Aided Drug Design Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
³⁰ GlaxoSmithKline, Collegeville, PA 19426, USA.
³¹ Agios Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
³² Bristol-Myers Squibb Research and Development, Pennington, NJ 08534, USA.
³³ Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
³⁴ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
³⁵ Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA.
³⁶ Merck Research Laboratories, West Point, PA 19486, USA.
³⁷ Janssen Pharmaceuticals, Inc., Spring House, PA 19002, USA.
³⁸ Science For Solutions, LLC, West Windsor, NJ 08550, USA.
³⁹ CEITEC-Central European Institute of Technology and National Centre for Biomolecular Research, Masaryk University Brno, 625 00 Brno, Czech Republic.
⁴⁰ Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
⁴¹ Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
⁴² Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
⁴³ Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK.
⁴⁴ Astex Pharmaceuticals, Cambridge CB4 0QA, UK.

PMID: 27050687
PMCID: PMC5070601
DOI: 10.1016/j.str.2016.02.017

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

Paul D Adams et al. Structure. 2016.

. 2016 Apr 5;24(4):502-508.

doi: 10.1016/j.str.2016.02.017.

Authors

Affiliations

¹ Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley Laboratory, Department of Bioengineering, UC Berkeley, Berkeley, CA 94720-8235, USA.
² DART NeuroScience, LLC, San Diego, CA 92131, USA.
³ Bruker AXS, Inc., Madison, WI 53711, USA.
⁴ Schrödinger, Inc., New York, NY 10036, USA.
⁵ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁶ Biosystems and Biomaterials Division, NIST, Gaithersburg, MD 20899, USA.
⁷ Genentech, Inc., South San Francisco, CA 94080, USA.
⁸ National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, MD 20894, USA.
⁹ Global Phasing Ltd., Cambridge CB3 0AX, UK.
¹⁰ School of Biosciences, University of Kent, Canterbury CT2 7NH, UK; Charles River Ltd., Structural Biology and Biophysics, Cambridge CB10 1XL, UK.
¹¹ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences and San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: stephen.burley@rcsb.org.
¹² Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
¹³ Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
¹⁴ OpenEye Scientific, Cambridge, MA 02142, USA.
¹⁵ MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
¹⁶ Drug Design Data Resource and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: vfeher@ucsd.edu.
¹⁷ Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK. Electronic address: groom@ccdc.cam.ac.uk.
¹⁸ Structural Biology, Lilly Biotechnology Center, San Diego, CA 92121, USA.
¹⁹ Structural Biology Center, Biosciences, Argonne National Laboratory, Argonne, IL 60439, USA.
²⁰ Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
²¹ Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
²² Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²³ School of Chemistry & Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia.
²⁴ BioMagResBank, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, USA.
²⁵ Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²⁶ Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
²⁷ Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
²⁸ Protein Data Bank Japan, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
²⁹ Computer-Aided Drug Design Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
³⁰ GlaxoSmithKline, Collegeville, PA 19426, USA.
³¹ Agios Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
³² Bristol-Myers Squibb Research and Development, Pennington, NJ 08534, USA.
³³ Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
³⁴ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
³⁵ Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA.
³⁶ Merck Research Laboratories, West Point, PA 19486, USA.
³⁷ Janssen Pharmaceuticals, Inc., Spring House, PA 19002, USA.
³⁸ Science For Solutions, LLC, West Windsor, NJ 08550, USA.
³⁹ CEITEC-Central European Institute of Technology and National Centre for Biomolecular Research, Masaryk University Brno, 625 00 Brno, Czech Republic.
⁴⁰ Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
⁴¹ Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
⁴² Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
⁴³ Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK.
⁴⁴ Astex Pharmaceuticals, Cambridge CB4 0QA, UK.

PMID: 27050687
PMCID: PMC5070601
DOI: 10.1016/j.str.2016.02.017

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? 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.

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Figures

**Figure 1**
Example highlighting the value of presenting ligand electron density model fit and geometrical analysis from CCDC Mogul from the Global Phasing Buster Report (PDB ID: 2H7P, later superseded by entry 4TZT (He et al., 2006); CCD ID: 468).

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources