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Validation of Protein–Ligand Crystal Structure Models: Small Molecule and Peptide Ligands

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Protein Crystallography

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1607))

Abstract

Models of target proteins in complex with small molecule ligands or peptide ligands are of significant interest to the biomedical research community. Structure-guided lead discovery and structure-based drug design make extensive use of such models. The bound ligands comprise only a small fraction of the total X-ray scattering mass, and therefore particular care must be taken to properly validate the atomic model of the ligand as experimental data can often be scarce. The ligand model must be validated against both the primary experimental data and the local environment, specifically: (1) the primary evidence in the form of the electron density, (2) examined for reasonable stereochemistry, and (3) the chemical plausibility of the binding interactions must be inspected. Tools that assist the researcher in the validation process are presented.

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Acknowledgments

BR receives partial support from the Austrian Science Foundation (FWF) under project P28395-B26.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA

    Edwin Pozharski

  2. Stanford ChEM-H, Macromolecular Structure Knowledge Center, Stanford University, Shriram Center, 443 Via Ortega, Room 097, MC5082, Stanford, CA, 94305-4125, USA

    Marc C. Deller

  3. k.-k. Hofkristallamt, 991 Audrey Place, Vista, CA, 92084, USA

    Bernhard Rupp

  4. Department of Genetic Epidemiology, Medical University Innsbruck, Schöpfstr. 41, Innsbruck, 6020, Austria

    Bernhard Rupp

Authors
  1. Edwin Pozharski
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  2. Marc C. Deller
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  3. Bernhard Rupp
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Corresponding author

Correspondence to Bernhard Rupp .

Editor information

Editors and Affiliations

  1. Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, Maryland, USA

    Alexander Wlodawer

  2. Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, Illinois, USA

    Zbigniew Dauter

  3. Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan, Poland

    Mariusz Jaskolski

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Pozharski, E., Deller, M.C., Rupp, B. (2017). Validation of Protein–Ligand Crystal Structure Models: Small Molecule and Peptide Ligands. In: Wlodawer, A., Dauter, Z., Jaskolski, M. (eds) Protein Crystallography. Methods in Molecular Biology, vol 1607. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7000-1_25

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  • DOI: https://doi.org/10.1007/978-1-4939-7000-1_25

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6998-2

  • Online ISBN: 978-1-4939-7000-1

  • eBook Packages: Springer Protocols

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