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? 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.
authors.affiliation: Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley Laboratory, Department of Bioengineering, UC Berkeley, Berkeley, CA 94720-8235, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
authors.affiliation: DART NeuroScience, LLC, San Diego, CA 92131, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Aertgeerts
authors.affiliation: Bruker AXS, Inc., Madison, WI 53711, USA.
authors.forename: Cary
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Schrödinger, Inc., New York, NY 10036, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bell
authors.affiliation: 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.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Berman
authors.affiliation: Biosystems and Biomaterials Division, NIST, Gaithersburg, MD 20899, USA.
authors.forename: Talapady N
authors.initials: TN
authors.lastname: Bhat
authors.affiliation: Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Blaney
authors.affiliation: National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, MD 20894, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Bolton
authors.affiliation: Global Phasing Ltd., Cambridge CB3 0AX, UK.
authors.forename: Gerard
authors.initials: G
authors.lastname: Bricogne
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NH, UK; Charles River Ltd., Structural Biology and Biophysics, Cambridge CB10 1XL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: 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.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Clark
authors.affiliation: OpenEye Scientific, Cambridge, MA 02142, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Darden
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emsley
authors.affiliation: 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.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Feher
authors.affiliation: 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.
authors.forename: Zukang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK. Electronic address: groom@ccdc.cam.ac.uk.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Groom
authors.affiliation: Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Seth F
authors.initials: SF
authors.lastname: Harris
authors.affiliation: Structural Biology, Lilly Biotechnology Center, San Diego, CA 92121, USA.
authors.forename: Jorg
authors.initials: J
authors.lastname: Hendle
authors.affiliation: Schrödinger, Inc., New York, NY 10036, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Holder
authors.affiliation: Structural Biology Center, Biosciences, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Kleywegt
authors.affiliation: Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Krojer
authors.affiliation: 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.
authors.forename: Joseph
authors.initials: J
authors.lastname: Marcotrigiano
authors.affiliation: School of Chemistry & Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mark
authors.affiliation: BioMagResBank, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Markley
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.affiliation: 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.
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Garib
authors.initials: G
authors.lastname: Murshudov
authors.affiliation: Protein Data Bank Japan, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Protein Data Bank Japan, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: OpenEye Scientific, Cambridge, MA 02142, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Nicholls
authors.affiliation: Computer-Aided Drug Design Group, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Nicklaus
authors.affiliation: GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Nolte
authors.affiliation: Agios Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Padyana
authors.affiliation: GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Peishoff
authors.affiliation: Bristol-Myers Squibb Research and Development, Pennington, NJ 08534, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Pieniazek
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Read
authors.affiliation: Research Collaboratory for Structural Bioinformatics Protein Data Bank, Center for Integrative Proteomics Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Shao
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Sheriff
authors.affiliation: Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Smart
authors.affiliation: Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Soisson
authors.affiliation: Janssen Pharmaceuticals, Inc., Spring House, PA 19002, USA.
authors.forename: John
authors.initials: J
authors.lastname: Spurlino
authors.affiliation: Science For Solutions, LLC, West Windsor, NJ 08550, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Stouch
authors.affiliation: CEITEC-Central European Institute of Technology and National Centre for Biomolecular Research, Masaryk University Brno, 625 00 Brno, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Svobodova
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.affiliation: Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Tronrud
authors.affiliation: Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Sameer
authors.initials: S
authors.lastname: Velankar
authors.affiliation: Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, UK.
authors.forename: Suzanna C
authors.initials: SC
authors.lastname: Ward
authors.affiliation: OpenEye Scientific, Cambridge, MA 02142, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Warren
authors.affiliation: 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.
authors.forename: John D
authors.initials: JD
authors.lastname: Westbrook
authors.affiliation: Astex Pharmaceuticals, Cambridge CB4 0QA, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Huanwang
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Young
mesh_terms: D018360:Crystallography, X-Ray; D066289:Data Curation; D030562:Databases, Protein; D017408:Guidelines as Topic; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins