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.

Agios Pharmaceuticals Inc Cambridge MA 02139 USA

Astex Pharmaceuticals Cambridge CB4 0QA UK

BioMagResBank Department of Biochemistry University of Wisconsin Madison Madison WI 53706 1544 USA

Bioscience Division Los Alamos National Laboratory Los Alamos NM 87545 USA

Biosystems and Biomaterials Division NIST Gaithersburg MD 20899 USA

Bristol Myers Squibb Research and Development Pennington NJ 08534 USA

Bristol Myers Squibb Research and Development Princeton NJ 08543 USA

Bruker AXS Inc Madison WI 53711 USA

Cambridge Crystallographic Data Centre Cambridge CB2 1EZ UK

CEITEC Central European Institute of Technology and National Centre for Biomolecular Research Masaryk University Brno 625 00 Brno Czech Republic

Center for Advanced Biotechnology and Medicine 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; Department of Molecular Biology and Biochemistry Rutgers The State University of New Jersey Piscataway NJ 08854 USA

Computer Aided Drug Design Group Center for Cancer Research National Cancer Institute National Institutes of Health Frederick MD 21702 USA

DART NeuroScience LLC San Diego CA 92131 USA

Department of Biochemistry and Biophysics Oregon State University Corvallis OR 97331 USA

Department of Chemistry and Chemical Biology 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; Center for Advanced Biotechnology and Medicine Rutgers The State University of New Jersey Piscataway NJ 08854 USA

Department of Haematology Cambridge Institute for Medical Research University of Cambridge Cambridge CB2 0XY UK

Department of Molecular Physiology and Biological Physics University of Virginia Charlottesville VA 22908 USA

Drug Design Data Resource and Department of Chemistry and Biochemistry University of California San Diego La Jolla CA 92093 USA

Genentech Inc South San Francisco CA 94080 USA

GlaxoSmithKline Collegeville PA 19426 USA

Global Phasing Ltd Cambridge CB3 0AX UK

Janssen Pharmaceuticals Inc Spring House PA 19002 USA

Merck Research Laboratories West Point PA 19486 USA

Molecular Biophysics and Integrated Bioimaging Division Lawrence Berkeley Laboratory Department of Bioengineering UC Berkeley Berkeley CA 94720 8235 USA

MRC Laboratory of Molecular Biology Cambridge CB2 0QH UK

National Center for Biotechnology Information U S National Library of Medicine Bethesda MD 20894 USA

Novartis Institutes for BioMedical Research Cambridge MA 02139 USA

OpenEye Scientific Cambridge MA 02142 USA

Protein Data Bank in Europe European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SD UK

Protein Data Bank Japan Institute for Protein Research Osaka University Osaka 565 0871 Japan

Research Collaboratory for Structural Bioinformatics Protein Data Bank Center for Integrative Proteomics Research Rutgers The State University of New Jersey Piscataway NJ 08854 USA

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

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

School of Biosciences University of Kent Canterbury CT2 7NH UK; Charles River Ltd Structural Biology and Biophysics Cambridge CB10 1XL UK

School of Chemistry and Molecular Biosciences University of Queensland St Lucia QLD 4072 Australia

Schrödinger Inc New York NY 10036 USA

Science For Solutions LLC West Windsor NJ 08550 USA

Structural Biology Center Biosciences Argonne National Laboratory Argonne IL 60439 USA

Structural Biology Lilly Biotechnology Center San Diego CA 92121 USA

Structural Genomics Consortium University of Oxford Oxford OX3 7DQ UK

Structural Genomics Consortium University of Toronto Toronto ON M5G 1L7 Canada

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Structural Analysis of Strigolactone-Related Gene Products

Validation of ligands in macromolecular structures determined by X-ray crystallography