Nucleic Acids Research, 2003, Vol. 31, No. 13 3856-3858
© 2003 Oxford University Press
Building protein diagrams on the web with the residue-based diagram editor RbDe
Lucy Skrabanek1,
Fabien Campagne*,1 and
Harel Weinstein1,2
1 Mount Sinai School of Medicine, Institute for Computational Biomedicine and Department of Physiology and Biophysics, New York, NY, USA
2 Weill Medical College of Cornell University, Physiology and Biophysics, New York, NY, USA
*To whom correspondence should be addressed. Tel: +1 212 327 7345; Fax: +1 212 327 7344; Email: fabien.campagne{at}mssm.edu
Received February 14, 2003; Revised and Accepted April 1, 2003
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ABSTRACT
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The residue-based diagram editor (RbDe) is web-based software
that greatly simplifies the construction of schematic diagrams
of proteins. Residue-based diagrams display the sequence of
a given protein in the context of its secondary and tertiary
structure. Such diagrams are frequently used to summarize mutations
or sequence features, in the context of the overall topology
of a protein. The initial version of RbDe was designed for transmembrane
proteins and has enabled many users to create diagrams of large
systems such as G protein-coupled receptors or transporters.
We present an extended diagram editor that supports other families
of proteins. Users can now import custom-diagram layouts, use
them to render members of any protein family and generate high-quality
output for publication purposes. RbDe is available free over
the web, at
http://icb.mssm.edu/crt/RbDe
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INTRODUCTION
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Residue-based diagrams of proteins, also called snake-like diagrams
or protein plots, are 2D representations of a protein sequence
that contains information about properties such as secondary
structure. Figure
1 shows an example of a diagram drawn with
the first release of RbDe. Since 1999, we have been developing
and maintaining the residue-based diagram editor (RbDe) to help
users create residue-based diagrams of transmembrane proteins
interactively. RbDe was designed from the ground up as a web
application and has been available freely over the web since
its initial release (
1,
2).
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Figure 1. Diagram of the human dopamine transporter. The diagram was produced through the web with the first release of RbDe. Residues are colored according to residue types (the color scheme colors residues of similar physicochemical properties in a similar way) and the diagram indicates the element of secondary structure (transmembrane helices) and the connecting loops. The white circles represent contiguous stretches of residues which are omitted from this diagram.
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Here we present a new release of RbDe that supports the interactive
creation of diagrams with custom layout.
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RELATED WORK
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Several programs have been developed to automate the rendering
of diagrams for membrane proteins or assist in their drawing.
Among these, Viseur (
http://transport.physbio.mssm.edu/viseur)
(
3,
4), VHMPT (
5) and RbDe, have focused on allowing users to
construct diagrams interactively and to adjust the parameters
that control the appearance of a diagram through a graphical
user interface. T
EXtopo (
6) focused on creating highly customizable
diagrams that can produce high quality output for publication.
High quality output could also be obtained with the Viseur program
when using the encapsulated postscript output, but customization
options were very limited in this program (Viseur was designed
mostly for proteins in the G protein-coupled receptor family).
T
EXtopo allows users to place labels on the diagram, add legend
and graphical annotations to certain residues and control to
some extent the appearance of loops. In order to use T
EXtopo,
users must be familiar with the LaTeX typesetting system (
7).
This is a factor that probably limits the applicability of this
tool.
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RbDe
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In contrast, RbDe was designed and implemented as a web application
and can be accessed from most web browsers. Figure
2 illustrates
how a user progresses through the software to create a diagram.
Since it was originally published in 2000 (
2), RbDe has been
used to create an average of five diagrams a day by registered
users from over 40 countries.
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Figure 2. Progression of a typical user through the web application for a typical use of RbDe. Information is collected as the user progresses through the sections of the web software (seq: sequence; ss: secondary structure; layout: layout of the diagram on the page, see text for details; colors: colors of specific residues or color scheme to color the entire diagram by residue type; URLs: hyperlinks from residues to documents on the web). The diagram is built and refined iteratively as the user proceeds through the application.
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CUSTOM LAYOUTS
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In the new extended version of RbDe, users can import a custom
diagram layout. The layout determines how sequences imported
in RbDe will be laid out in the final picture. In contrast to
the first version of RbDe, the extended version presented here
makes it possible to customize the overall placement of the
secondary structure elements in the diagram. This feature allows
users to customize layouts for a specific purpose, such as the
rendering of diagrams for a specific family of proteins, or
to refine the presentation of existing diagrams of transmembrane
proteins.
RbDe accepts layouts encoded as described for the residue-based diagram generator (RbDg) (8). The creation of a layout input file for RbDe requires knowledge of XML and a few conventions described in the RbDg XML schema documentation (see http://icb.mssm.edu/crt/RbDg). The development of a new diagram layout can be performed in an iterative manner, usually by trial and error, after an outline of the final layout has been created on paper. Figure 3 shows a fragment of an input file, and the corresponding fragment in the diagram produced by RbDe, as the layout directives are interpreted to render a sequence.
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Figure 3. (A) Fragment of a layout input file. A layout is defined by a list of subunits. Each subunit has a type, which determines how the residues in the subunit will be rendered. Some subunit types (e.g. helices and strands) are given a direction. The direction is a vector that controls the global direction along which residues of the subunit will be rendered. Other subunits, such as subunits to represent loops that connect the first type of subunits, are given a spacer. The spacer is a vector that defines how much the first residue of the subunit is separated from the last. Units of direction and spacer are pixels in the coordinate system shown on the right. (B) Fragment of a diagram built with the layout parameters shown on the left. Yellow arrows represent the direction of helices and strands. Green arrows represent the spacers of the loops.
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SCALABLE VECTOR GRAPHICS OUTPUT
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In addition to image outputs, RbDe can generate diagrams in
the scalable vector graphics (SVG) format (
http://www.w3.org/TR/SVG/).
SVG is a vectorial format that is gaining growing acceptance
as a standard for exchange of high-quality images, schemas and
diagrams on the web. Diagrams produced with RbDe can be exported
to SVG by clicking on a link in the diagram library (see menu
on the top of the application screens). The resulting SVG document
is visualized with an appropriate plug-in, and/or can be saved
to disk. The SVG document can be read in Adobe Illustrator (version
10+) or similar tools with SVG support. Since SVG is a vectorial
format, parts of the figure can be scaled, removed, re-colored
or altered in a variety of ways, to further customize the diagram,
for instance for publication purposes. (Diagrams shown in Figs
1,
3 and
4 were generated with RbDe and edited with Adobe Illustrator
10.)
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Figure 4. The calmodulin protein sequence is rendered and shown with two diagram layouts based on the crystal structure of the molecule (A) and the calmodulin-trifluoperazine complex (B). The diagrams reveal the structural rearrangement upon ligand binding.
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APPLICATION
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As an example of custom layout, we have built a diagram of the
rat calmodulin protein and its complexed form with trifluoperazine.
The diagrams were constructed in the following manner: the secondary
structure elements were determined with the Kabsch and Sander
algorithm (
9) from crystal structure in the Protein Data Bank
(PDB ID: 3CLN
[PDB]
and 1A29
[PDB]
). Visual inspection of the 3D structures
suggested an arrangement for the secondary structure elements
in the 2D diagram. The layouts were further adjusted to eliminate
superposition of residues. An RbDg input file was then built
iteratively for each conformation of the protein, using as a
guide the initial sketch, and visualizing the diagram after
adding each helix or strand. Creating a diagram layout is possible
over the web, but for faster iterations we recommend using a
local installation of the diagram generator. The final layout
portion of the RbDg input file can then be uploaded to RbDe
and used to plot proteins that share the same secondary structure.
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ACKNOWLEDGEMENTS
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This work was supported in part by NIH grants P01 DA124080
[GenBank]
,
P20 HL69733 and the Institute for Computational Biomedicine
at MSSM.
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REFERENCES
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- Campagne,F., Jestin,R., Reversat,J.L., Bernassau,J.M. and Maigret,B. (1999) Visualisation and integration of G protein-coupled receptor related information help the modelling: description and applications of the Viseur program. J. Comput. Aided Mol. Des., 13, 625–643.[CrossRef][Web of Science][Medline]
- Konvicka,K., Campagne,F. and Weinstein,H. (2000) Interactive construction of residue-based diagrams of proteins: the RbDe web service. Protein Eng., 13, 395–396.[Abstract/Free Full Text]
- Campagne,F. (1995) The Viseur Program. http://transport.physbio.mssm.edu/viseur. Laboratoire de Chimie Theorique, Nancy, France.
- Campagne,F. and Weinstein,H. (1999) Schematic representation of residue-based protein context-dependent data: an application to transmembrane proteins. J. Mol. Graph. Model., 17, 207–213.[CrossRef][Web of Science][Medline]
- Lin,W.J. and Hwang,M.J. (1998) VHMPT: a graphical viewer and editor for helical membrane protein topologies. Bioinformatics, 14, 866–868.[Abstract/Free Full Text]
- Beitz,E. (2000) T(E)Xtopo: shaded membrane protein topology plots in LAT(E)X2epsilon. Bioinformatics, 16, 1050–1051.[Abstract/Free Full Text]
- Lamport,L. (1994) LaTeX: A Document Preparation System, 2nd Ed., Addison Wesley.
- Campagne,F., Bettler,E., Vriend,G. and Weinstein,H. (2003) Batch mode generation of residue-based diagrams of proteins. Bioinformatics, in press.
- Kabsch,W. and Sander,C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 22, 2577–2637.[CrossRef][Web of Science][Medline]
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