Structural biology has played a central role in fueling the massive advances made by the life sciences in the last few decades. More than a dozen Nobel prizes have been awarded for achievements in structural biology since solution of the structure of the DNA double helix in the early 1950s was followed by solution of the first protein structures at the end of the same decade. Beautiful images of three-dimensional structures regularly adorn the covers of Science
. Indeed, a wealth of protein structures has been solved in recent years, and entries in the Protein Data Bank (PDB) [1
] now number over 50,000. But structural information is surprisingly still not in the mainstream of biology for the simple reason that three-dimensional structures are often hard to understand, even for a structural biologist. The widely held impression is that these structures are understood in detail and put to use in research; in fact, the structures are hardly discussed at all, especially by biologists lacking a structural background. While computer graphics software greatly aids in the understanding of these structures by displaying them in three-dimensions, the pages of printed scientific journals flatten the structures to a two-dimensional image, with much of the three-dimensional information thus being lost. It should be noted, however, that a number of journals (Nature
, Nature Structural and Molecular Biology
, ACS Chemical Biology
and Molecular Biosystems
) have begun to offer links to FirstGlance in Jmol [3
] for interactive three-dimensional structure visualization, and two journals (ACS Chemical Biology
and Biochemical Journal
) occasionally offer interactive three-dimensional figures crafted by Molecules In Motion [4
]; but these still lack the simple direct link between the printed information and the three-dimensional structures that is provided by Proteopedia
. Moreover, many biologists have a limited knowledge of chemistry; thus, structural biologists need to make a special effort to develop tools that make macromolecular structures accessible and useful to the life science and clinical communities.
One such tool is molecular animation. Movies are successful at making biomacromolecules and their complexes come to life on the screen, and thus are often able to preserve and convey three-dimensional information far better than static two-dimensional images. Previous efforts to communicate the structural and functional features of a biomacromolecule have largely focused on creation of such movies and on interactive visualizations (for example, Kinemage [5
], MovieMaker [6
], Protein Explorer [7
], Protein Movie Generator [9
], and PDB2MGIF [10
]). Until recently, the time and technical knowledge required to make such macromolecular animations were daunting. This has been partly rectified with the advent of eMovie [12
], a plug-in for the molecular visualization program PyMOL [13
], and PolyView3D [14
], which have both simplified the creation process and lowered the threshold for sharing molecular three-dimensional information via movies. However, although movies are excellent for individual presentations, they are not an adequate solution to the problem that we are attempting to address, because they are fixed once created, and provide neither an interactive environment nor integration with textual information.
What is missing is a common resource that would make three-dimensional structures easier to understand, permit linking of function to structure, and at the same time simplify the sharing of structural information. This should be accomplished not by reducing the amount of information conveyed, but rather by making three-dimensional information intuitive, and thus more accessible to all. Already, valuable attempts have been made to tackle this problem. Perhaps the most notable recent example is iSee [16
], which, like Kinemage, makes three-dimensional structures more intuitive by linking textual information to three-dimensional views of the structure. However, iSee uses both proprietary authoring tools, which must be purchased, and a proprietary viewer that has to be downloaded and installed in order to view both text and three-dimensional structures.
For non-structural biologists, the issue is not understanding a structure as an end in itself, but relating the structural information to biological applications: for example, how do mutations cause disease? Or, to be more specific, what mutation can be performed that will prevent one protein from interacting with another? How can one design a drug that will stabilize a protein destabilized by mutagenesis? Which part of a protein may be useful as an epitope? What happens in an organism in which a given protein domain is missing? In order for structural biology to provide genuine added value for non-structural biologists, we need a resource that will allow the relevant information and its analysis to be entered by the appropriate, knowledgeable scientists - and easily accessed and understood by users without a formal background in structural biology.
is a wiki-based web-resource that has been designed to address what is missing from structural biology: a mechanism for making three-dimensional structures easier to understand, a linking of function to interactive three-dimensional structure visualization, and a simplified sharing of structural and functional knowledge (a wiki is a resource or website where users can edit the pages in the website using simple text-editing tools). This resource is a tool for all scientists who need to utilize three-dimensional structural information in their research, as well as for educators requiring a medium for compelling presentation of structure-function relationships. Proteopedia
is also meant for structural biology specialists in need of a more effective method of communicating their results. As a website, Proteopedia
is freely accessible to all users without the need for downloading and installing any software. (Java is required. Most users will find that they already have Java installed on their computers. Should they need to download Java, they will be directed to the Java website for the free and simple download.). Furthermore, adding content to the website is simple: textual content is added in the same way as it is added in Wikipedia [17
], taking advantage of an interface that is familiar to millions. Interactive, customized scenes of three-dimensional structures linked to the text are simple to add via Proteopedia
's easy-to-use Scene Authoring Tools
is intended to be the website of first-resort for everyone from research scientists to students seeking integrated three-dimensional structural and functional information about a particular protein or molecule.
has three defining features. First, three-dimensional information is presented in an intuitive manner: descriptive text contains hyperlinks that change the adjacently displayed three-dimensional structures to coincide with points made in the text. (Figure ). (The visualizations in Proteopedia
are, in fact, not truly three-dimensional, but the impression of three-dimensionality is achieved by having the structure rotate, a visualization technique pioneered by Levinthal in the 1970s [18
].) Second, there is no requirement for installation and operation of downloadable viewers. A web browser is all that is needed for full access, including both interactive three-dimensional viewing and content authoring. The site works equally well on Windows, Mac OS X, and Linux. Third, content can be easily added by any approved, knowledgeable user, via simple-to-use authoring tools.
Figure 1 Green links change from one easily authored molecular scene to another. (a) For example, a user interested in hemoglobin visits the page of that name in Proteopedia (see ), which then loads with a slowly rotating crystal structure of hemoglobin in (more ...)