Proteopedia, 3D molecules with a real time edge

Abstract

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Proteopedia, 3D molecules with a real time edge

Rădoi Valentin*, Vârgolici Bogdana*
*University of Medicine and Pharmacy “Carol Davila”
Correspondence to: Rădoi Valentin, Student,
Str. Aleea Poiana Sibiului, Nr. 4, Bl. MC1, Sc. 1, Et. 8, Ap. 88, Bucharest, Romania
Phone: +40 743 18 34 45, Email: ilumma.conquer@yahoo.co.uk
Total Word Count: 3105

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Proteopedia, 3D molecules with a real time edge

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Structural biology has played a central role in fueling the massive advances made by the
life sciences in the last few decades, with more than a dozen Nobel prizes being awarded for
achievements in structural biology in the last half century. As such, to fully understand three-
dimensional structures, as well as use them in research, a good comprehension of the structure
of the biomacromolecule is needed. A molecular visualization tool provides just that.

Proteopedia offers exactly this, coming with several advantages, such as a full
representation for the entire Protein Data Bank database. All this, whilst being open source and
available on any platform due its MediaWIki core. Each user may improve any page available
on Proteopedia, but quality control still exists because you need an account which is given only
to researchers, professors and students. Not the least of all, molecular visualization can be used
as a learning tool, to help students better understand what they learn and also complete
assignments using the Scene Authoring Tools.

So far Proteopedia has seen a permanent advance, with more and more users
contributing to it and the software winning 2010 The Scientist "Best Science Website" Labby
Awards, as well as being used as an Interactive 3D Complement by the Journal of Biological
Inorganic Chemistry for each of their macromolecular structure papers. Proteopedia pages can
now also be submitted to the Journal of Biochemistry and Molecular Biology Education
(BAMBED) for peer-review and publication.

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Keywords: Proteopedia, Molecular Visualization, Biochemistry, Molecular Biology,
Graphics

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The need for 3D
Structural biology has played a central role in fueling the massive advances made by the
life sciences in the last few decades, with more than a dozen Nobel prizes being awarded for
achievements in structural biology in the last half century [1]. As such, especially in the last
years, with the huge advancement of computer use in research, numerous new
macromolecules have had their structures totally deciphered. This, coupled with the huge
number of small non-peptide potential drug candidates easily available (over 7 million
compounds), highlights the need of using computer-aided techniques for efficient identification
and optimization of novel hit compounds [2].
On the other hand, one of the main problems in teaching many of the life sciences such
as biochemistry, molecular biology, immunology, both at a high school, and a college
level, as well as in research, is the difficulty in achieving a conceptual understanding[3].
Although 2d pictures are widely available at this moment, the main problem is the loss of three-
dimensional information due to the flattening of the structure. Also, a 3D structure has 6 faces,
so to be able to fully see it in 2D; you would need six 2D pictures and additional information so
you are able to fully correlate them. For medical students, for example, learning a structure is
not an end in itself, but relating the structural information to biological information: what
mutations prevent one protein from interacting with another? What happens in an organism in
which a given protein domain is missing? What is the importance of the 3D structure of a protein
and of the chaperone that determines it? [1, 4].
The internet is a powerful communication medium increasingly exploited by business
and science alike, especially in structural biology and bioinformatics. The traditional
presentations of static 2D images of real-world objects on the limited medium of paper can now

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be shown interactively in three dimensions [5]. The internet has already started being used as a
platform for sharing new biomacromolecules structures through the Protein Data Bank (PDB)
website, which is the single worldwide archive of structural data of biological macromolecules
[6].
The main two types of tools available on the internet for molecular animations are
movies and visualization programs. Previous efforts to communicate the structural and
functional features of a biomacromolecules through movies have been plagued by the fact that
the time and technical knowledge required to make such macromolecular animations were
daunting in programs like MovieMaker [7], ProteinExplorer [8], ProteinMovieGenerator [9] and
PDB2MGIF [10]. Although, the technical aspects have become easier with recent programs,
such as eMovie [11], movies still are fixed once created, and provide neither an interactive
environment nor integration with textual information.
The second solution, represented by visualization programs, exemplified by iSee [12],
solved this problem, making 3D structures more intuitive by linking textual information to 3D
views of the structure. However, the use of proprietary authoring tools, which must be bought,
and of proprietary viewers that need to be downloaded and installed deter a lot of users.

Five reasons for Proteopedia

Proteopedia is a molecular visualization tool, integrated in a fully working website, built
on a Wikipedia core (mediawiki [13]), which is free to use, does not require any additional
software and can be easily modified by users, whilst maintaining a strong quality control.

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Three Dimensional Representations for the entire PDB database
The entire PDB databank, composed of over 67000 biomacromolecules, is represented
in an intuitive, fully 3D medium.
The first thing you can notice is the visualization of the structure you choose, which
seems three dimensional due to its rotation [14]. The structure isn’t a movie, as it can be
manually rotated in any direction and you can zoom in and out, using the mouse. The original
visualization can be modified by choosing to only see parts of it, by clicking the text under it. In
this way you can choose to observe only the small or the large ribosomal unit, like in Figure 1.
Depending on the biomacromolecules you are visualizing and its functionality, numerous
choices can be made, each structure having its own possibilities for display.
All the biomacromolecules with deciphered structures are also accompanied by the
abstract of the article which appeared on its discovery, as taken from Pubmed. Numerous
biomacromolecules of importance are accompanied by much larger texts, with scientific
references and several visualizations, which focus on important parts of the structure, using
proteopedia’s features, such as zooming in on a specific part of the structure, using
transparency, changing the way chains are seen, as well their color, adding or removing other
molecules etc. The text can also include green hyperlinks that highlight key parts of the
structure.
The 3d visualizations are programmed in JMol, one of the leading applications in the
field, which is also open source [15].The structures are calculated in real time, being based on
psychical forces and chemical interactions, which allows a bigger freedom for the developers
and which could prove very useful in further development.
The content on Proteopedia is updated weekly with the new addition to the PDB
database and it extends beyond the contents of the PDB, providing for hierarchical organization

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of structure and function categories such as protein families, structural classes and biological
functions [1].

Fully open source and available on any platform

Proteopedia is developed on the open source MediaWiki core [13], using JMol for
graphical representation [15] and only requiring Java to be installed on your computer. As such,
it can work on any platform ( Windows, Linux, Mac ) and on all the browsers ( Firefox, Internet
Explorer, Google Chrome, Opera ), even without internet access, as each structure, with the
accompanying text and representations, can be downloaded through one click directly from that
structure main page. The small size of each of these downloads (several megabits), make
Proteopedia suitable for direct use in courses and presentations and it also allows users who
don’t have access to broad bandwidth, as in underdeveloped states, to access it easily.
Proteopedia can be used freely by anyone, including professors, researchers and
students. The success of open source initiatives, such as Proteopedia, came from their fast
growth, based on the numerous persons from all over the world who helped each project
develop [16].

Proteo”wiki”pedia

Due to its build, each page available on the site can be improved by a user, in a true wiki
fashion. Modifications become visible and searchable immediately. Adding and editing content

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is quick, easy and accessible to the common non-technical user and scientist. As such mistakes
and errors can be corrected fast and easily and , through the option , available for any user, to
receive e-mail notification when a certain page is modified, the developers made sure that any
change is checked in short time from its making and that any mistakes that may appear are
corrected just as fast.
Each change made to a page is logged in that page’s history, so that pages can easily
be reverted to a previous state. If needed, a page can be locked so that only a handful of users
can evaluate and accept changes proposed to that page. As such, the quality of the information
is kept [1].
One of the main problems of Wikis is quality control, because anyone can change the
information. Proteopedia solved this problem by adding several safeguards. Whilst anybody can
view the entire content of Proteopedia, to edit it you will need an account, which is only given to
researchers, professors and students. What is different from other wikis is the fact that once you
contribute to a page, your real name is added, under your real name, as Proteopedia Page
Contributor and Editor. As such, it is easier to seed out the person who made the mistake and it
also gives the authors credit for their work. These features, combined with the ones presented
earlier, such as page history, easy modification of errors, page locking allow a high quality of the
content present on Proteopedia.

A learning tool

Proteopedia was designed to also help students better understand the structures and
functions of biomacromolecules. Apart from its obvious utility as a teaching instrument due to

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the integration of all known biomacromolecular structures, Proteopedia can be used in several
different ways as a teaching instrument.
By allowing students to also create pages and through the ease of use of the Scene
Authoring Tools, which allows anyone to use the full power of Proteopedia, assignments such
as this one (http://proteopedia.org/wiki/index.php/Photosystem_II) can be easily accomplished
by students, with minimal computer knowledge. Whole courses, including examinations, can be
made by teachers (Examples: http://www.umass.edu/microbio/chime/). The main advantage of
using Proteopedia, instead of classical methods, is the fact that, instead of learning the structure
and the function of a biomacromolecule by heart, the student understands that they are closely
related and the teacher can test this, as in Figure 2.
The existence of protected pages, which can’t be edited by anyone else, and of sandbox
pages, which are deleted after a short period of time and can be recognized because their name
starts with “sandbox_”, allows students to work in a safe and hassle free environment, where
they can learn how to use Proteopedia to the fullest. For ease of access, professors can even
reserve a batch of sandbox pages for their students.

Advantages of Proteopedia over other molecular visualization softwares

Several other free visualization softwares have appeared in the meantime, such as
PDBWiki [17], ProteinDBS [18], Kinemage [19,21], TOPSAN [20].
A thorough comparison between these resources can be seen in Table 1. As can be
seen by comparing the table available in this article with a similar one from [1], which presents

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some of the same visualization softwares and their characteristics from April 2008, we can see
that most of the resources are going in two directions.
On one hand most of these resources are going towards a ‘wiki’ style, integrating user
friendly authoring tools, like Proteopedia has included since the starts, whilst, on the other hand,
we see the appearance of specialized databases. One example in this direction is ProteinDBS,
which allows for protein comparison, using the publishers’ servers and showing a visual 2D
comparison between the original protein the match(es) found. [18]

Conclusions

So far Proteopedia has seen a permanent advance, with more and more users
contributing to it and the software winning 2010 The Scientist "Best Science Website" Labby
Awards, as well as being used as an Interactive 3D Complement by the Journal of Biological
Inorganic Chemistry for each of their macromolecular structure papers [22,23]. Proteopedia
pages can now also be submitted to the Journal of Biochemistry and Molecular Biology
Education (BAMBED) for peer-review and publication.

Sources Of Funding:
None;
Disclosures:
None;

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References


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10. Bohne A PDB2MultiGIF: A Web ToPDB2MultiGIF: a web tool to create animated images
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11. Hodis E, Schreiber G, Rother K, Sussman JL eMovie: a storyboard-based tool for
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20. Weekes D, Krishna SS, Bakolitsa C, Wilson IA, Godzik A, Wooley J., TOPSAN: a
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Figure 1.1 The entire Ribosome, as described by Venkatraman Ramakrishnan of the M.R.C.
Laboratory of Molecular Biology in Cambridge, England; Thomas A. Steitz of Yale University;
and Ada E. Yonath of the Weizmann Institute of Science in Rehovot, Israel which have been
awarded the 2009 Nobel Prize in Chemistry, showing the tRNAs, mRNA, rRNA, proteins,
Aminoacyl(A)-site tRNA ,Peptidyl(P)-site tRNA, Exit(E)-site tRNA, the large subunit and the
small subunit.

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Figure 1.2 A minimal representation, showing only the large subunit of the ribosome (See Figure
1.1)


Visualizatio
n Software

Purpose Contents
(September
2010)
Web
resourc
e
Contains
all entries
in the
PDB,
updated
automatic
ally
Commu
nity
annotati
on
Interacti
ve 3D
within
site with
molecul
ar
scenes
linked to
text
User-
friendl
y 3D
authori
ng
tools,
freely
availab
le.
Proteopedi
a

A free,
collaborativ
e, three-
dimensiona
l
encycloped
ia of
proteins
and other
One page for
every PDB
entry with
abstract and
interactive
three-
dimensional
views,
including
functional
Yes Yes Yes Yes Yes