Nucleic Acids Research 2005 33(Database issue):D233-D237;
doi:10.1093/nar/gki057
Nucleic Acids
Research, 2005, Vol. 33, Database issue D233-D237
© 2005, the authors
Nucleic
Acids Research, Vol. 33, Database issue © Oxford University Press 2005; all
rights reserved
The RCSB Protein Data Bank: a redesigned query system and relational
database based on the mmCIF schema
Nita
Deshpande1, Kenneth J. Addess1,
Wolfgang F. Bluhm1, Jeffrey C.
Merino-Ott1, Wayne Townsend-Merino1,
Qing Zhang1, Charlie Knezevich1,
Lie Xie1, Li Chen3, Zukang
Feng3, Rachel Kramer Green3,
Judith L. Flippen-Anderson3, John
Westbrook3, Helen M. Berman3 and
Philip E. Bourne1,2,*
1 San Diego Supercomputer Center and 2 Department of
Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla,
CA 92093, USA and 3 Department of Chemistry and Chemical Biology,
Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ
08854-8087, USA
* To whom correspondence should be addressed. Tel:
+1 858 534 8301; Fax: +1 858 822 0873; Email: bourne{at}sdsc.edu
Received September 15, 2004; Revised and Accepted October 1,
2004
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ABSTRACT |
The
Protein Data Bank (PDB) is the central worldwide repository for
three-dimensional (3D) structure data of biological macromolecules.
The Research Collaboratory for Structural Bioinformatics (RCSB)
has completely redesigned its resource for the distribution and
query of 3D structure data. The re-engineered site is currently in
public beta test at http://pdbbeta.rcsb.org/. The new site
expands the functionality of the existing site by providing
structure data in greater detail and uniformity, improved query
and enhanced analysis tools. A new key feature is the integration
and searchability of data from over 20 other sources covering
genomic, proteomic and disease relationships. The current
capabilities of the re-engineered site, which will become the RCSB
production site at http://www.pdb.org/ in late 2005, are
described.
 |
INTRODUCTION |
The
production version of the Research Collaboratory for Structural
Bioinformatics Protein Data Bank (RCSB PDB) (http://www.pdb.org/) is mirrored at
seven sites around the world and has been described previously (1,2). In order to improve the
accessibility of the PDB's structure data, display the increased
level of detail and improved consistency resulting from the RCSB PDB
data uniformity project (3,4), and take advantage of
advances in database and Web/Internet technologies, the RCSB PDB has
re-engineered its database and redesigned the associated website.
This site is now available for beta testing at http://pdbbeta.rcsb.org/ and will
henceforth be referred to as PDB Beta. The following features of PDB
Beta have been introduced: software architecture, database content
and schema, data integration from other sources, and query and
analysis capabilities expanded from those reported previously (5).
|
CONTENT |
Software
architecture, database content and schema
Using an Enterprise Java
framework, the PDB Beta has been redesigned and it is composed of
three tiers: an underlying relational database, a presentation tier
designed in collaboration with users and an object-relational J2EE
middle tier based on Hibernate. The PDB Beta has been tested with
both MySQL and IBM DB2 relational database tiers. The current system
uses MySQL, which enables unlimited distribution of the primary and
secondary data in the RCSB PDB database. Moreover, the current system
makes extensive use of freely distributable Java components (Table 1).
The
database uses an mmCIF-based (6) schema derived from
the PDB Exchange Dictionary (7). Data are loaded from
either XML (8)
or mmCIF data files with their associated remediated and extended
content. Data file parser/structure loaders are SQL-92 compliant and
therefore independent of the backend database. Data files are parsed
and loaded weekly at the same time as the current production site is
updated. The design of this system along with its local weekly data
updates will facilitate local distribution and use.
Data integration from other sources
From a user's
perspective, macromolecular structure does not exist in isolation,
but is generally associated with an inquiry that might include
relationships to genomic and proteomic sequence, biological function,
cellular location and disease. While the focus of the RCSB PDB
remains on fully exposing the features of macromolecular structures,
a wider spectrum of inquiry is now possible. This is achieved through
the weekly collection and integration (warehousing) of external data.
For example, data from the Gene Ontology (GO) (9), Enzyme Commission (http://www.chem.qmul.ac.uk/iubmb/enzyme/),
KEGG Pathways (10,11) and NCBI resources
(including LocusLink, OMIM, SNP and BookShelf) (12) are mapped onto
structures and loaded into the database. This is achieved as
follows.
Our ongoing data uniformity efforts enable accurate assignment of
external database references to structures in the RCSB PDB database;
these include identifiers from Swiss-Prot (13), GenBank,
PubMed, EC numbers and the taxonomy of the source organism.
These references are used to locate information in a further
set of databases. For example, Swiss-Prot identifiers were used
to assign GO terms from the Gene Ontology Consortium to structures.
Swiss-Prot and GenBank identifiers were also used to obtain
genome information: gene name, chromosome location, structural
genomics targets (14) and OMIM numbers for
structures. Figure
1 summarizes the rich and varied linkages that have been
established between structure data in the RCSB PDB database and data
from external biological databases. Note that many of these data
are related to structure through a one-to-many relationship
since a structure consists of one or more components, such as
multiple polypeptide chains. The representation of structures
as a number of constituent components, each with external data
assignments, is an ongoing effort at the RCSB PDB.
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Figure 1. Primary and secondary
references assigned to structures. The primary references are
assigned during structure annotation/data curation. Secondary
references are collected from external databases using the primary
reference identifiers and accession numbers. This is rerun on a
weekly basis for new and all existing structures and stored in the
database.
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Data
loaders written in Java access the external databases, parse the
files and load relevant derived information into the database. In
some instances additional external information is retrieved at query
run time. For example, KEGG pathways associated with a given EC
number are retrieved by issuing a Web service call to the KEGG
database at query run time. Under an agreement with the US National
Library of Medicine, PubMed identifiers for the primary citation
associated with a structure are used to load the PubMed abstracts
into the RCSB PDB database. In doing so, abstracts can be searched by
keyword(s) as an alternative means to find structures of
interest.
As a final example of how linkages between incorporated data were
generated, consider the relationship between structure and disease
(Figure 2). The OMIM
text was searched for disease terms obtained from the chapter and
section headings in the online book Genes and Disease from the NCBI
Bookshelf (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.preface.91).
The disease term and the OMIM numbers returned for the term
were loaded into a relational table, as was a mapping of structures
to OMIM numbers from the Swiss-Prot site. The two tables were
joined using OMIM numbers and the disease term was thus mapped
onto structures. These relationships have enabled the implementation
of a hierarchical disease tree suitable for browsing. For example,
users can locate all the PDB structures identified as being
associated with cancer and drill down to find only those associated
with breast cancer.
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Figure 2. Procedure to create
structure-OMIM-disease mapping. Disease terms listed in the NCBI
book Genes and Disease are used to mine the OMIM text for OMIM
numbers associated with the terms. This Disease-OMIM mapping is
loaded into the database. Performing a join on the Disease-OMIM
table created above and the OMIM-Structure mapping table results in
Disease-Structure mapping.
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Query
and analysis
Browsing
A
major feature of PDB Beta is the ability to browse database content.
Much of the data now integrated with structure is hierarchical and
lends itself to display via tree browsers. When each node in a
browser tree is moused over, the number of associated structures at
that branch is displayed. This gives the user a sense of the size of
the result set, even before a query is made. As some data that are
browsed are not strictly hierarchical, concessions are made. An
example of this concession is a protein chain that has been
associated with multiple GO molecular functions. This protein chain
would therefore appear multiple times in the browser tree even though
it is only associated with a single structure. Browsers are also
useful in reverse; knowing the location of a structure in a tree
reveals its place in the hierarchy. For example, entering homo
sapiens in the taxonomy browser will locate the structures for
which this has been identified as a source organism, and highlight
where humans are located in the tree of life, at least according to
the NCBI classification scheme. The results of browsing can be used
as a starting point for query refinement using the SearchFields
interface outlined below.
Searching
The PDB Beta has retained
the search capability of the RCSB PDB production site but has
provided, based on user feedback, more intuitive interfaces and added
additional Website navigation tools. Sequence searching functionality
via BLAST (15) has
also been added.
SearchLite is based on the Lucene text indexing and search engine,
and uses the content of the mmCIF versions of the PDB structures
which provides indexes of terms not available in the original
PDB files. For example, at the time of submission it may not
have been known that the structure was associated with apoptosis.
When the term is later added to the list of Swiss-Prot keywords,
it will be accessible through SearchLite even though there was
no reference in the original PDB file. SearchLite can be considered
as an inclusive rather than an exclusive search engine, since
it produces results that may require further query refinement.
This feature is also available on the current production site.
StatusSearch continues to provide information on deposited but
unreleased structures. Sequence data are available ahead of a
structure's release for some entries, which is useful for theoretical
modeling and avoiding duplication of effort.
SearchFields, an interface for performing advanced queries, has
been enhanced to include the full extent of the experimental
information that is collected and much of the integrated information
outlined above. Particular attention has been paid to NMR structures.
A new SearchFields option is to search for structures with specific
NMR experimental parameters like refinement method, selection
criteria, spectrometer details and sample conditions.
Searches performed during a session are recorded and can be
recalled and rerun or modified and rerun. Since the result of
one query may trigger a new line of inquiry, we have extended
the notion of query by example in which a result from one
query can be used as a search term in a subsequent query. For
example, a search for the structure with the PDB identifier 1AEW
[PDB] displays the Structure Explorer page for the iron
storage molecule ferritin (16). According to the GO
term for the single polypeptide chain in the asymmetric unit of this
structure, it is assigned a molecular function of ‘ferric iron
binding’. Clicking on this term on the Structure Explorer page will
reveal all other structures in the PDB associated with the same
molecular function as defined by the same GO term.
A histogram feature in the early stages of development is applied
to quantitative data and is accessible from the results display.
For example, an X-ray structure is reported with a resolution
of 2.5 Ĺ. A novice user may be interested in how that
resolution compares with the contents of the complete database.
An icon next to the resolution on the structure page can be
selected to present a graphical distribution of the resolutions
of all the structures in the PDB. Specific ranges can be expanded
and the structures in a selected resolution range displayed in
a report format.
The PDB Beta is also composed of ![~]()
1000 curated Web
pages, which have been made more accessible through site searching
and indexing. All features are in the process of being better
documented and made accessible through a context-sensitive help
system based on the RoboHelp tool.
Results reporting
Query results are
presented on the Structure Explorer page for a single structure or in
the Query Results Browser for a set of structures. The Structure
Explorer page presents data similar to the format of a scientific
paper. This page can be printed as a PDF. Table 2 highlights the new
features that are included beyond those available from the current
production site. Of the new reports, the Materials and Methods
section is customized based on the experiment type. Structure
Explorer pages list crystallization, diffraction and refinement
information for X-ray structures; and NMR experiment, refinement and
ensemble information for NMR entries.
Molecular
viewers
Recognizing the difficulties that users may have
installing the existing molecular viewers, four new, general purpose
molecular viewers have been added to the PDB Beta: KiNG, Jmol,
SimpleViewer and WebMol applets. KiNG, Jmol and WebMol require
Java-enabled browsers; SimpleViewer requires the installation of
Java3D to provide high-quality rendering. SimpleViewer is an example
of an application built from the Molecular Biology Toolkit (MBT)
(http://mbt.sdsc.edu/). The concept
behind MBT is to deliver simple context-sensitive molecular graphics
applications at the appropriate point in a query. So for example, a
ligand viewer has been implemented that provides a detailed view of
the interaction between a macromolecule and a ligand (HET group in
original PDB terminology), but is not designed to be a
general-purpose molecular viewer. A SNPviewer, indicating where
non-synonymous single nucleotide polymorphisms (SNPs) are mapped onto
structures, is another example of the use of a context-sensitive
viewer that has been added to the PDB Beta.
Distribution system
The RCSB production and PDB Beta
sites distribute data files in the PDB, mmCIF and XML formats. Data
for sequences and complete structural descriptions are available in
uncompressed as well as various compressed formats. The PDB data can
also be obtained using CORBA and Web services. A CORBA server may be
established using C++ (http://deposit.pdb.org/mmcif/FILM/)
or the Java OpenMMS software (http://openmms.sdsc.edu/) (17). Web services,
which are currently in the early implementation stage, will
allow users to use XML and SOAP to perform queries and retrieve
results programmatically from the PDB Beta. The PDB Beta Web
Services Definition Language (WSDL) is available at http://pdbbeta.rcsb.org/jboss-net/services/pdbWebService?wsdl.
|
CONCLUSION |
While the
RCSB PDB's primary mandate continues to be the delivery of
high-quality structure data in a timely manner, our services are
being expanded. Recognizing that structure exists as a point on a
spectrum of biological inquiry, more integrated access to structure
data is being provided. Using PDB Beta locally to manage private
copies of the PDB data on a laptop or larger computer, and a web
interface that can be customized for individual user preferences,
either locally or on the RCSB's PDB servers are examples of
forthcoming deliverables. Comments and suggestions are always welcome
by sending email to betafeedback{at}rcsb.org
. Upon completion of the beta testing, anticipated to be in late
2005 the re-engineered site will be available as the PDB production
site (http://www.pdb.org/).
|
ACKNOWLEDGEMENTS |
The RCSB PDB is
operated by Rutgers, The State University of New Jersey; the San
Diego Supercomputer Center (SDSC) at the University of California San
Diego (UCSD); and the Center for Advanced Research in Biotechnology
(CARB/UMBI/NIST)—three members of the Research Collaboratory for
Structural Bioinformatics. This work is supported by grants from
National Science Foundation (NSF), National Institute of General
Medical Sciences (NIGMS), Office of Science, Department of Energy
(DOE), National Library of Medicine (NLM), National Cancer Institute
(NCI), National Center for Research Resources (NCRR), National
Institute of Biomedical Imaging and Bioengineering (NIBIB) and
National Institute of Neurological Disorders and Stroke (NINDS). The
RCSB PDB is a member of wwwPDB. We wish to thank the many users who
have provided input into the development of the re-engineered
RCSB PDB.
|
Notes
|
The
online version of this article has been published under an open
access model. Users are entitled to use, reproduce, disseminate, or
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purposes provided that: the original authorship is properly and fully
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given; if an article is subsequently reproduced or disseminated not
in its entirety but only in part or as a derivative work this must be
clearly indicated. For commercial re-use permissions, please contact
journals.permissions{at}oupjournals.org
.
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CONTENT
TOP
INTRODUCTION
