Technology Report
`
`pubs.acs.org/jchemeduc
`
`RCSB Protein Data Bank: A Resource for Chemical, Biochemical,
`and Structural Explorations of Large and Small Biomolecules
`†,§
`‡,§
`†,§
`Christine Zardecki,*,†,§
`Shuchismita Dutta,
`David S. Goodsell,
`Maria Voigt,
`†,§,∥,⊥,#
`and Stephen K. Burley
`†
`Center for Integrative Proteomics Research and Department of Chemistry and Chemical Biology, Rutgers, The State University
`of New Jersey, 174 Frelinghuysen Road, Piscataway, New Jersey 08854, United States
`‡
`Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037,
`United States
`§RCSB Protein Data Bank
`∥
`Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, New
`Jersey, 08854, United States
`⊥
`Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla,
`California 92093-0657, United States
`#San Diego Supercomputer Center, University of California, San Diego, 10100 Hopkins Dr, La Jolla, California, 92093
`
`ABSTRACT: The Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) supports scientific
`research and education worldwide by providing access to annotated information about three-dimensional (3D) structures of
`macromolecules (e.g., nucleic acids, proteins), and associated small molecules (e.g., drugs, cofactors, inhibitors) in the PDB
`archive. Researchers, educators, and students use RCSB PDB resources to study the shape and interactions of biological
`molecules and their implications in molecular biology, medicine, biotechnology, and beyond. RCSB PDB supports development
`of standards for data deposition, representation, annotation, and validation of atomic structural data obtained from various
`experimental methods. Uniform representation of PDB data is essential for providing consistent search and analysis capabilities
`for all PDB users, from beginning students to domain experts. The RCSB PDB Web site provides tools for searching, visualizing,
`and analyzing PDB data, including easy exploration of chemical interactions that stabilize macromolecules and play important
`roles in their interactions and functions. In addition, educational resources are available for free and unrestricted use in the
`classroom for exploring chemistry and biology at the molecular level.
`KEYWORDS: General Public, High School/Introductory Chemistry, First-Year Undergraduate/General,
`Graduate Education/Research, Biochemistry, Interdisciplinary/Multidisciplinary, Internet/Web-Based Learning,
`Nucleic Acids/DNA/RNA, Proteins/Peptides, X-ray Crystallography
`
`T he Protein Data Bank (PDB) is the first open access
`
`digital resource in biology for sharing three-dimensional
`(3D) protein structures.1 The PDB was established in 1971 with
`7 structures, and has grown exponentially to provide access to
`more than 113,000 entries of natural and designed macromole-
`cules (proteins, nucleic acids and carbohydrates), more than
`84,000 of which are complexed with small chemical components
`(solvent molecules,
`ions, cofactors,
`inhibitors, and drugs).
`Originally, PDB was a resource designed for the structural
`biology community, but through the years, its utility has grown
`and the PDB users now include biologists, software developers,
`computational and other scientists, bioinformaticians, students,
`educators and the general public.
`The PDB archive of data files is one of the most heavily
`used biological data resources worldwide. In 2014, more than
`505,000,000 atomic coordinate and experimental data files were
`downloaded for research and education. These downloads also
`include routine downloads by pharmaceutical and biotechnology
`companies for use in proprietary drug discovery efforts. A huge
`number of free resources and tools utilize PDB data to serve
`their users. These range from educational resources such as the
`
`NIH 3D Print Exchange2 and Proteopedia;3 molecular viewers
`including Jmol/JSmol,4 Chimera,5 Pymol;6 and many scientific
`research tools and databases.7
`The PDB archive is managed by a collection of regional data
`centers, called the Worldwide Protein Data Bank (wwPDB),8
`spread across the United States, Europe, and Japan. wwPDB
`centers collaborate on data deposition and annotation/validation
`practices. Each member hosts a distribution center, and provides
`tools for access and usage. Research Collaboratory for Structural
`Bioinformatics (RCSB) PDB, based at Rutgers, The State
`University of New Jersey and the University of California, San
`Diego,
`is focused on providing resources for research and
`education.9 As part of the wwPDB, RCSB PDB members curate
`PDB data and develop data standards and software for the depo-
`sition and annotation pipeline. RCSB PDB also aims to enable
`breakthroughs in scientific inquiry, medicine, drug discovery, and
`technology by offering tools that provide rich structural views
`
`Special Issue: Chemical Information
`
`Published:
`
`January 6, 2016
`
`© 2016 American Chemical Society and
`Division of Chemical Education, Inc.
`
`569
`
`DOI: 10.1021/acs.jchemed.5b00404
`J. Chem. Educ. 2016, 93, 569−575
`
`Downloaded via 216.241.254.30 on October 12, 2023 at 03:13:34 (UTC).
`
`See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
`
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`KELONIA EXHIBIT 1024
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`Journal of Chemical Education
`
`Table 1. Data Dictionaries Used in PDB Biocuration
`
`Technology Report
`
`Resource
`
`PDB Exchange (PDBx)/macromolecular Crystallo-
`graphic Information File (mmCIF) Dictionary
`http://mmcif.wwpdb.org (accessed 6 Nov 2015)
`Chemical Component Dictionary (CCD) http://
`www.wwpdb.org/data/ccd (accessed 6 Nov 2015)
`
`Biologically Interesting molecule Reference
`Dictionary (BIRD) http://www.wwpdb.org/data/
`bird (accessed 6 Nov 2015)
`
`Description
`
`Crystallographic data dictionaries with extensions describing NMR, 3DEM, and protein production, contains >4300 data
`items
`
`Each chemical definition includes descriptions of chemical properties such as stereochemical assignments, chemical
`descriptors (SMILES16 and InChI21), systematic chemical names, and idealized coordinates (generated using Molecular
`Networks’ Corina, and if there are issues, OpenEye’s OMEGA). Contains >18,000 small molecules
`Molecular weight and formula, polymer sequence and connectivity, descriptions of structural features and functional
`classification, natural source (if any), and external references to corresponding UniProt or Norine entries. Contains
`∼750 small molecules
`
`of biological molecules and systems. In addition to supporting
`biological and chemical learning, RCSB PDB is an exemplar of
`the new discipline of data science; it provides a glimpse into
`science history, and serves as a resource for developing database
`query and analysis skills.
`In this paper, we describe data annotation practices, and
`highlight RCSB PDB resources available for query and analysis,
`and education.
`
`■ ARCHIVING PDB DATA: DEPOSITION,
`ANNOTATION, AND VALIDATION
`The PDB archive includes 3D structures of macromolecules
`(primarily proteins, DNA and RNA) as determined by experi-
`ments using X-ray crystallography, nuclear magnetic resonance
`(NMR), and/or 3D electron microscopy (3DEM). For each new
`structure, researchers submit atomic coordinates, experimental
`data, and molecular information using specialized tools, and
`wwPDB biocurators then review, annotate and validate the
`entry. Atomic coordinates are checked for consistency with
`the known sequence of the macromolecule and chemical
`structure of small molecules, and biological assemblies are
`defined and annotated. The entry is also extensively annotated
`with experimental information and cross-referenced to related
`entries and external
`resources. The wwPDB collaborates
`closely with archives that maintain related data, including the
`Cambridge Structural Database of small molecule crystal
`structures,10 and the EMDataBank for 3D Electron Microscopy
`maps and models.11
`Uniform annotation of PDB data enables consistent search-
`ing and analysis across the archive. To facilitate uniformity,
`PDB curation relies upon standard data dictionaries that define
`the representation of all components in the entry (Table 1).
`While the PDB Exchange (PDBx)12 and macromolecular Crys-
`tallographic Information File (mmCIF)13 data dictionaries pro-
`vide the bases for internal data cross-referencing, processing,
`annotation, validation and database management operations,
`the Chemical Component Dictionary14 describes all standard
`and modified amino acids/nucleotides, small molecule ligands,
`and solvent molecules. All chemical components are checked
`against this dictionary during annotation.17 Protein and nucleic
`acid polymers can be built by linking together individual chemical
`components in a specified order denoted by the polymer
`sequence. Specialized molecules with unusual chemistries and
`interesting biological and pharmaceutical
`functions, such as
`peptide-like inhibitors and many antibiotics, are included in the
`Biologically Interesting molecule Reference Dictionary.15 Use of
`these dictionaries enables specialized query and access to small
`molecule information, from specialized information pages for
`all ligands in the PDB to tools for visualizing ligand−protein
`interactions.
`wwPDB uses community-accepted standards to “validate”
`deposited data, and produces reports that provide an assessment
`
`of structure quality based upon geometric and experimental
`data validation. wwPDB has convened method-specific Validation
`Task Forces18 to develop recommendations for validation stan-
`dards and software for use in annotation.19 During annotation,
`validation reports are provided to the depositor to highlight any
`areas of concern. Journal editors may request these reports from
`authors to inform manuscript review.
`The PDB archive includes structural information with a wide
`range of quality, due to the many challenges inherent in the
`experimental methods, and the nature of
`the molecule(s)
`or complex(es) being studied. Validation reports for all PDB
`structures determined by X-ray crystallography include a
`“slider” graphic (Figure 1) to summarize the quality of the
`
`Figure 1. Validation report slider graphic indicates the quality of an
`entry as compared with other PDB entries. Shown is the slider image
`for an entry with better overall quality relative to all X-ray structures
`(PDB entry 1cbs, a small protein with a ligand at 1.8 Å resolution).20
`
`determined structure as compared with other structures in the
`archive. These graphics are displayed on the RCSB PDB Web
`site to help users find the structures of highest quality and to
`provide a warning to be critical when using structures with less
`experimental support.
`
`■ QUERY, REPORTING, AND ANALYSIS
`The RCSB PDB Web site21 integrates PDB data, related infor-
`mation about the structure from external scientific resources,
`and precalculated comparative and statistical
`information for
`query, analysis, and visualization.22 On average, the Web site is
`accessed by ∼325,000 unique users every month from ∼190
`countries. The top search bar supports simple keyword searches
`(ID, author, molecule name, chemical name), and suggests results
`options organized by different categories,
`including organism,
`molecule name, or experimental technique. Advanced searching
`allows users to combine searches for many specific data items,
`such as molecule name, authors, experimental techniques, and
`resolution. Browsers are available to find PDB structures
`organized using data annotations from external resources
`(e.g., Gene Ontology terms describing biological process, cellular
`component, and molecular function;23 Enzyme Classification;24
`the World Health Organization Collaborating Centre’s Anatom-
`
`570
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`Figure 2. Structure Summary page highlights for PDB entry 4qgi, an HIV protease complexed with the drug saquinavir.29 (A) PDB ID, title, 2D
`image with links to interactive 3D viewers; (B) information about the publication describing the entry, with links to PubMed and reference
`information; (C) small molecule information with links to summary information and 3D views. Structure Summary pages also include links to the
`atomic coordinates, sequence information, experimental data, and validation information.
`
`ical Therapeutic Chemical (ATC) Classification System); or
`by exploring drill-down distributions of standard characteristics
`(e.g., polymer type, organism, resolution). Since general searches,
`such as for “hemoglobin”, can return hundreds of matching
`structures, a variety of tools are available to help narrow the
`focus of the inquiry. For example, search autosuggestions, query
`refinement options, and sorting results by most recently solved
`entry, molecular weight, and resolution can help guide users to
`structures of higher quality and relevance. When available,
`searches will also return corresponding educational Molecule
`of the Month features, which are described in more detail below.
`Every entry has a Structure Summary page that provides
`access to many aspects of the structure (Figure 2). Interactive
`3D viewers, including Jmol/JSmol and Ligand Explorer,25 can
`be used to rotate the molecule, select specific residues, and
`highlight ligand−protein interactions.4 Many of the data items
`shown can be used to query for other entries with the same data
`(e.g., sequence database reference, specific chemical component).
`The entry’s corresponding validation slider described above
`
`(Figure 1) is also displayed. Additional links provide related
`information from external scientific sources, such as functional
`annotations from CATH26 and SCOP,27 and sequence infor-
`mation from UniProt.28
`The RCSB PDB Web site also supports small molecule
`searching by ID, name, formula, or chemical drawing. Summary
`pages are available for each chemical component to provide 2D
`and 3D visual representations, any subcomponent information,
`corresponding DrugBank7d information, and access to atomic
`coordinates (Figure 3).
`Additionally, the RCSB PDB Mobile app supports access to
`molecular data on mobile devices (Android and iOS).30 App
`users can search the entire PDB database by ID, molecule name,
`or author name, and view a summary report for corresponding
`structures. The 3D visualization program NDKMol31 allows app
`users to interactively view structures and save views as images.
`The app can be used to search and explore structures during
`lectures, symposia, and poster sessions.
`
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`Figure 3. Ligand summary for ATP. The information shown on this page is built using the corresponding entry for ATP contained in the Chemical
`Component Dictionary. Blue text links to “query-by-example” searches of the archive, and may be used to find entries that include the ligand. Data
`highlighted in orange are integrated from external resources such as DrugBank to provide any pharmaceutical context to the structure not included in
`the deposited PDB entry.7d The top ligand image can be downloaded, and the 3D view of the molecule rotated using Jmol.4
`
`■ EDUCATIONAL RESOURCES
`
`A recent survey revealed that the RCSB PDB Web site is
`used by a wide range of communities,
`including educators
`and students at the high school and university levels. For the
`educational community, RCSB PDB tools take a subject-based
`approach, allowing chemistry students to visualize the chemical
`and structural basis of biological processes, such as how is
`oxygen stored and transported to different cells in the human body
`or how do specific drugs act on their target proteins. Tools are
`available to find and visualize PDB molecules of interest and
`explore their interactions. In addition, a number of resources
`provide nonexperts with information and examples of how to
`interpret the molecule’s functions in the context of chemical
`interactions.
`To enable broader access by educators and students, RCSB
`PDB established an education-focused portal to PDB data.
`The PDB-101 Web site32 hosts regularly published articles,
`educational materials, and introductions to information specific
`to PDB data and their representations within the archive.
`The Molecule of the Month column33 serves as the founda-
`tion of many PDB-101 resources. Since 2000, this feature has
`highlighted selected biological structures with text, images, and
`interactive views (Figure 4). The column provides a curated set
`of example structures from the archive to illustrate key points
`about a molecule. The collection of Molecule of the Month
`articles has been organized by biological concept into a browser
`to enable top-down searching by functional category. Rather
`than searching by a particular molecule, users can browse
`articles about specific topics (such as viruses or the immune
`system).
`Beyond Molecule of the Month, PDB-101 offers a wide range
`of educational materials to explore biomolecular structure and
`
`Figure 4. Images from the Molecule of the Month column on HIV
`Capsid.34 (A) The feature begins with a description of the general biology,
`with an illustration of a single capsid protein (left; PDB entry 1e6j)35 and
`the full capsid (right; 3j3q).36 (B) A description of molecules that interact
`with the HIV capsid follows, showing TRIM5 (2lm3)37 and cyclophilin
`(1ak4).38 (C) The final section presents a JSmol39 view to allow interactive
`exploration of the HIV capsid hexamer (3mge)40 and pentamer (3p05).41
`
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`popular areas of research selected were the life sciences (66%),
`chemistry (34%), and computational sciences (20%). Examples of
`how these PDB-related materials have been incorporated at the
`collegiate level are frequently highlighted in our Education Corner,
`a guest column published in our quarterly newsletter. Examples
`have included drug discovery projects,44 interesting molecular
`visualizations,45 and cell biology.46 The usage of PDB data and the
`utility of accurate molecular visualizations in undergraduate educa-
`tion has been a topic of much study.47 Other published examples
`of undergraduate classroom usage include 3D printing and
`models,48 molecular modeling,49 pharmaceutical and medicinal
`chemistry,50 and beyond.51
`■ CONCLUSION
`
`The RCSB PDB offers free access to a broad range of primary
`research data and educational materials for all users. Structural
`entries in the PDB are extensively annotated and validated
`according to current community standards, providing a rich
`resource for chemical exploration. With the RCSB PDB tools
`and resources, users may explore detailed information about
`small and large biomolecules, their chemical interactions, as well
`as study broader structural and functional concepts in biology.
`
`■ AUTHOR INFORMATION
`
`Corresponding Author
`*E-mail: Zardecki@rcsb.rutgers.edu.
`Notes
`The authors declare no competing financial interest.
`
`■ ACKNOWLEDGMENTS
`
`RCSB PDB is funded by the NSF (DBI-1338415), NIH, and
`DOE. The RCSB PDB is a member of the Worldwide PDB
`along with PDB in Europe, PDB Japan, and BioMagResBank.
`
`■ REFERENCES
`
`(1) (a) Berman, H. M.; Kleywegt, G. J.; Nakamura, H.; Markley, J. L.
`How community has shaped the Protein Data Bank. Structure 2013, 21
`(9), 1485−91. (b) Protein Data Bank. Crystallography: Protein Data
`Bank. Nat. New Biol. 1971, 233 (42), 223.
`(2) NIH 3D Print Exchange. http://3dprint.nih.gov/ (accessed 6
`Nov 2015).
`(3) Prilusky, J.; Hodis, E.; Canner, D.; Decatur, W. A.; Oberholser,
`K.; Martz, E.; Berchanski, A.; Harel, M.; Sussman, J. L. Proteopedia: a
`status report on the collaborative, 3D web-encyclopedia of proteins
`and other biomolecules. J. Struct. Biol. 2011, 175 (2), 244−52.
`(4) Jmol: an open-source Java viewer for chemical structures in 3D.
`http://www.jmol.org/ (accessed 6 Nov 2015).
`(5) Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.;
`Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera–a
`visualization system for exploratory research and analysis. J. Comput.
`Chem. 2004, 25 (13), 1605−12.
`(6) DeLano, W. The PyMOL molecular graphics system, http://
`www.pymol.org (accessed 6 Nov 2015).
`(7) (a) Kirchmair, J.; Markt, P.; Distinto, S.; Schuster, D.; Spitzer, G.
`M.; Liedl, K. R.; Langer, T.; Wolber, G. The Protein Data Bank
`(PDB), its related services and software tools as key components for in
`silico guided drug discovery. J. Med. Chem. 2008, 51 (22), 7021−40.
`(b) Berman, H. M.; Kleywegt, G. J.; Nakamura, H.; Markley, J. L. The
`Protein Data Bank archive as an open data resource. J. Comput.-Aided
`Mol. Des. 2014, 28, 1009−1014. (c) Fernandez-Suarez, X. M.; Rigden,
`D. J.; Galperin, M. Y. The 2014 Nucleic Acids Research Database Issue
`and an updated NAR online Molecular Biology Database Collection.
`Nucleic Acids Res. 2014, 42 (Database issue), D1−6. (d) Law, V.;
`Knox, C.; Djoumbou, Y.; Jewison, T.; Guo, A. C.; Liu, Y.; Maciejewski,
`
`573
`
`DOI: 10.1021/acs.jchemed.5b00404
`J. Chem. Educ. 2016, 93, 569−575
`
`Figure 5. Exploring the structure of fluorescent proteins. Images
`from the GFP activity at PDB-101. (A) Ribbon view of GFP with the
`chromophore highlighted in its core, based on entry 1ema.42 (B) Close-
`up of specific residues chemically linked to form the chromophore.
`(C) A downloadable PDF can be used to create a paper model of GFP.
`Curated JSmol view of GFP highlights (D) conserved residues in the
`protein core that play a role in the chromophore formation and (E) the
`same structure superimposed with a distant relative DsRed (PDB
`entry 1g7k),43 showing high structure conservation despite limited
`sequence similarity.
`
`function. Videos and animations explore specific topics, from
`the biology of HIV to protein folding. Understanding PDB Data
`offers a general introduction to structural biology and PDB data
`files, with topics such as crystallographic resolution and bio-
`logical assemblies. Hands-on model activities can be used to
`explore the folding of proteins and nucleic acids.
`Resources have been compiled to provide activities, lesson
`plans, and curricula. For example,
`the Green Fluorescent
`Protein (GFP) activity (Figure 5) references the GFP Molecule
`of the Month, and uses a paper model to provides a hands-on
`understanding of the polymer nature of the protein, overall
`shape and folding of the protein, and the assembly of the GFP
`chromophore from chemical interactions between three specific
`amino acids in the core of the protein. An interactive JSmol
`view demonstrates the chemistry involved in the creation of
`chromophore.
`In December 2014, high school curricula were launched
`at PDB-101 to combine a variety of PDB-101 and external
`resources (videos, animations, games, activities and exercises)
`for comprehensive learning about the biology of HIV/AIDS at
`introductory and advanced high school
`levels. Using these
`materials, classes studied the HIV lifecycle, interactions with the
`immune system, and the basis of current infection treatments.
`Web site materials were accessed more than 8000 times during
`this pilot session. Based on feedback from high school instructors
`who participated in the pilot, the curricula have been reorganized
`into individual modules (Biomolecular Structures and Models,
`Molecular Immunology, Molecular View of HIV/AIDS) that can
`be implemented in a variety of other lesson plans. Development
`of similar modules focusing on the structural basis of diabetes is
`underway.
`PDB-101 is also used as a resource in college education. In a
`2014 survey of PDB-101 usage, 28% of respondents were under-
`graduate students, and 33% were graduate students. The most
`
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`

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`
`A.; Arndt, D.; Wilson, M.; Neveu, V.; Tang, A.; Gabriel, G.; Ly, C.;
`Adamjee, S.; Dame, Z. T.; Han, B.; Zhou, Y.; Wishart, D. S. DrugBank
`4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014,
`42 (Database issue), D1091−7. (e) Wassermann, A. M.; Bajorath, J.
`BindingDB and ChEMBL: online compound databases for drug
`discovery. Expert Opin. Drug Discovery 2011, 6 (7), 683−7. (f) Hu, L.;
`Benson, M. L.; Smith, R. D.; Lerner, M. G.; Carlson, H. A. Binding
`MOAD (Mother Of All Databases). Proteins: Struct., Funct., Genet.
`2005, 60 (3), 333−40. (g) Galperin, M. Y.; Rigden, D. J.; Fernandez-
`Suarez, X. M. The 2015 Nucleic Acids Research Database Issue and
`molecular biology database collection. Nucleic Acids Res. 2015, 43
`(Database issue), D1−5.
`(8) Berman, H. M.; Henrick, K.; Nakamura, H. Announcing the
`worldwide Protein Data Bank. Nat. Struct. Biol. 2003, 10 (12), 980.
`(9) Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.
`N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data
`Bank. Nucleic Acids Res. 2000, 28 (1), 235−42.
`(10) Allen, F. H. The Cambridge Structural Database: a quarter of a
`million crystal structures and rising. Acta Crystallogr., Sect. B: Struct. Sci.
`2002, 58 (3), 380−8.
`(11) Lawson, C. L.; Baker, M. L.; Best, C.; Bi, C.; Dougherty, M.;
`Feng, P.; van Ginkel, G.; Devkota, B.; Lagerstedt, I.; Ludtke, S. J.;
`Newman, R. H.; Oldfield, T. J.; Rees, I.; Sahni, G.; Sala, R.; Velankar,
`S.; Warren, J.; Westbrook, J. D.; Henrick, K.; Kleywegt, G. J.; Berman,
`H. M.; Chiu, W. EMDataBank.org: unified data resource for CryoEM.
`Nucleic Acids Res. 2011, 39 (Database issue), D456−64.
`(12) Westbrook, J.; Henrick, K.; Ulrich, E. L.; Berman, H. M. 3.6.2
`The Protein Data Bank exchange data dictionary. In International
`for Crystallography. Vol. G. Definition and Exchange of
`Tables
`Crystallographic Data; Hall, S. R., McMahon, B., Eds.; Springer:
`Dordrecht, The Netherlands, 2005; pp 195−198.
`(13) Fitzgerald, P. M. D.; Westbrook, J. D.; Bourne, P. E.; McMahon,
`B.; Watenpaugh, K. D.; Berman, H. M. 4.5 Macromolecular dictionary
`(mmCIF). In International Tables for Crystallography G. Definition and
`Exchange of Crystallographic Data; Hall, S. R., McMahon, B., Eds.;
`Springer: Dordrecht, The Netherlands, 2005; pp 295−443.
`(14) Westbrook, J. D.; Shao, C.; Feng, Z.; Zhuravleva, M.; Velankar,
`S.; Young,
`J. The chemical component dictionary: complete
`descriptions of constituent molecules in experimentally determined
`3D macromolecules in the Protein Data Bank. Bioinformatics 2015, 31
`(8), 1274−8.
`(15) Dutta, S.; Dimitropoulos, D.; Feng, Z.; Persikova, I.; Sen, S.;
`Shao, C.; Westbrook, J.; Young, J.; Zhuravleva, M. A.; Kleywegt, G. J.;
`Berman, H. M. Improving the representation of peptide-like inhibitor
`and antibiotic molecules in the Protein Data Bank. Biopolymers 2014,
`101 (6), 659−68.
`(16) Weininger, D. SMILES 1. Introduction and encoding rules. J.
`Chem. Inf. Model. 1988, 28, 31−36.
`(17) Young, J. Y.; Feng, Z.; Dimitropoulos, D.; Sala, R.; Westbrook,
`J.; Zhuravleva, M.; Shao, C.; Quesada, M.; Peisach, E.; Berman, H. M.
`Chemical annotation of small and peptide-like molecules at
`the
`Protein Data Bank. Database 2013, 2013, bat079.
`(18) (a) Read, R. J.; Adams, P. D.; Arendall, W. B., 3rd; Brunger, A.
`T.; Emsley, P.; Joosten, R. P.; Kleywegt, G. J.; Krissinel, E. B.; Lutteke,
`T.; Otwinowski, Z.; Perrakis, A.; Richardson, J. S.; Sheffler, W. H.;
`Smith, J. L.; Tickle, I. J.; Vriend, G.; Zwart, P. H. A new generation of
`crystallographic validation tools for the protein data bank. Structure
`2011, 19 (10), 1395−412. (b) Henderson, R.; Sali, A.; Baker, M. L.;
`Carragher, B.; Devkota, B.; Downing, K. H.; Egelman, E. H.; Feng, Z.;
`Frank, J.; Grigorieff, N.; Jiang, W.; Ludtke, S. J.; Medalia, O.; Penczek,
`P. A.; Rosenthal, P. B.; Rossmann, M. G.; Schmid, M. F.; Schroder, G.
`F.; Steven, A. C.; Stokes, D. L.; Westbrook, J. D.; Wriggers, W.; Yang,
`H.; Young, J.; Berman, H. M.; Chiu, W.; Kleywegt, G. J.; Lawson, C. L.
`Outcome of
`the first electron microscopy validation task force
`meeting. Structure 2012, 20 (2), 205−14. (c) Montelione, G. T.;
`Nilges, M.; Bax, A.; Guntert, P.; Herrmann, T.; Richardson, J. S.;
`Schwieters, C. D.; Vranken, W. F.; Vuister, G. W.; Wishart, D. S.;
`Berman, H. M.; Kleywegt, G. J.; Markley, J. L. Recommendations of
`the wwPDB NMR Validation Task Force. Structure 2013, 21 (9),
`
`Technology Report
`1563−70. (d) Trewhella, J.; Hendrickson, W. A.; Kleywegt, G. J.; Sali,
`A.; Sato, M.; Schwede, T.; Svergun, D. I.; Tainer, J. A.; Westbrook, J.;
`Berman, H. M. Report of the wwPDB Small-Angle Scattering Task
`Force: data requirements for biomolecular modeling and the PDB.
`Structure 2013, 21 (6), 875−81.
`(19) Gore, S.; Velankar, S.; Kleywegt, G. J. Implementing an X-ray
`validation pipeline for the Protein Data Bank. Acta Crystallogr., Sect. D:
`Biol. Crystallogr. 2012, 68 (4), 478−83.
`(20) Kleywegt, G. J.; Bergfors, T.; Senn, H.; Le Motte, P.; Gsell, B.;
`Shudo, K.; Jones, T. A. Crystal structures of cellular retinoic acid
`binding proteins I and II in complex with all-trans-retinoic acid and a
`synthetic retinoid. Structure 1994, 2 (12), 1241−58.
`(21) Heller, S.; McNaught, A.; Stein, S.; Tchekhovskoi, D.; Pletnev, I.
`InChI
`-
`the worldwide chemical structure identifier standard.
`J.
`Cheminf. 2013, 5 (1), 7.
`(22) Rose, P. W.; Prlic, A.; Bi, C.; Bluhm, W. F.; Christie, C. H.;
`Dutta, S.; Green, R. K.; Goodsell, D. S.; Westbrook, J. D.; Woo, J.;
`Young, J.; Zardecki, C.; Berman, H. M.; Bourne, P. E.; Burley, S. K.
`The RCSB Protein Data Bank: views of structural biology for basic and
`applied research and education. Nucleic Acids Res. 2015, 43 (Database
`issue), D345−56.
`(23) The Gene Ontology Consortium. Gene Ontology: tool for the
`unification of biology. Nat. Genet. 2000, 25, 25−29.
`(24) Nomenclature Committee of
`the International Union of
`Biochemistry and Molecular Biology (NC-IUBMB) Enzyme Nomen-
`clature: Recommendations of the Nomenclature Committee of the
`International Union of Biochemistry and Molecular Biology on the
`Nomenclature and Classification of Enzymes by the Reactions they
`Catalyse. http://www.chem.qmw.ac.uk/iubmb/enzyme (accessed 6
`Nov 2015).
`(25) Moreland, J. L.; Gramada, A.; Buzko, O. V.; Zhang, Q.; Bourne,
`P. E. The Molecular Biology Toolkit (MBT): a modular platform for
`developing molecular visualization applications. BMC Bioinf. 2005, 6
`(1), 21.
`(26) Sillitoe, I.; Cuff, A. L.; Dessailly, B. H.; Dawson, N. L.; Furnham,
`N.; Lee, D.; Lees, J. G.; Lewis, T. E.; Studer, R. A.; Rentzsch, R.; Yeats,
`C.; Thornton,
`J. M.; Orengo, C. A. New functional
`families
`(FunFams) in CATH to improve the mapping of conserved functional
`sites to 3D structures. Nucleic Acids Res. 2013, 41 (Database issue),
`D490−8.
`(27) Fox, N. K.; Brenner, S. E.; Chandonia, J. M. SCOPe: Structural
`Classification of Proteins–extended, integrating SCOP and ASTRAL
`data and classification of new structures. Nucleic Acids Res. 2014, 42
`(Database issue), D304−9.
`(28) The UniProt Consortium. Activities at the Universal Protein
`Resource (UniProt). Nucleic Acids Res. 2014, 42 (Database issue),
`D191−8.
`(29) Goldfarb, N. E.; Ohanessian, M.; Biswas, S.; McGee, T. D., Jr.;
`Mahon, B. P.; Ostrov, D. A.; Garcia, J.; Tang, Y.; McKenna, R.;
`Roitberg, A.; Dunn, B. M. Defective hydrophobic sliding mechanism
`and active site expansion in HIV-1 protease drug resistant variant
`Gly48Thr/Leu89Met: mechanisms for the loss of saquinavir binding
`potency. Biochemistry 2015, 54 (2), 422−33.
`(30) Quinn, G. B.; Bi, C.; Christie, C. H.; Pang, K.; Prlic, A.; Nakane,
`T.; Zardecki, C.; Voigt, M.; Berman, H. M.; Bourne, P. E.; Rose, P. W.
`RCSB PDB Mobile: iOS and Android mobile apps to provide data
`access and visualization to the RCSB Protein Data Bank. Bioinformatics
`2015, 31 (1), 126−7.
`(31) Nakane, T. Molecular Visualization, Online and On-the-Go.
`RCSB PDB Newsletter 2013, 56, http://bit.ly/1WM3XTv (accessed 6
`Nov 2015).
`(32) RCSB PDB, pdb101.rcsb.org (accessed 6 Nov 2015).
`(33) Goodsell, D.; Dutta, S.; Zardecki, C.; Voigt, M.; Berman, H.;
`Burley, S. The RCSB PDB “Molecule of the Month”: Inspiring a
`Molecular View of Biology. PLoS Biol. 2015, 13, e1002140.
`(34) Goodsell, D. S., HIV Capsid. RCSB PDB Molecule of the Month
`2013, 163, DOI: 10.2210/rcsb_pdb/mom_2013_7 (accessed 6 Nov
`2015).
`
`574
`
`DOI: 10.1021/acs.jchemed.5b00404
`J. Chem. Educ. 2016, 93, 569−575
`
`Page 6 of 7
`
`

`

`Journal of Chemical Education
`
`(35) Monaco-Malbet, S.; Berthet-Colominas, C.; Novelli, A.; Battai,
`N.; Piga, N.; Cheynet, V.; Mallet, F.; Cusack, S. Mutual conformational
`adaptations in antigen and antibody upon complex formation between
`an Fab and HIV-1 capsid protein p24. Structure 2000, 8 (10), 1069−
`77.
`(36) Zhao, G.; Perilla, J. R.; Yufenyuy, E. L.; Meng, X.; Chen, B.;
`Ning, J.; Ahn, J.; Gronenborn, A. M.; Schulten, K.; Aiken, C.; Zhang,
`P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-
`atom molecular dynamics. Nature 2013, 497 (7451), 643−6.
`(37) Biris,