Proteopedia - a scientific 'wiki' bridging the rift between three-dimensional structure and function of biomacromolecules

Abstract

Many scientists lack the background to fully utilize the wealth of solved three-dimensional biomacromolecule structures. Thus, a resource is needed to present structure/function information in a user-friendly manner to a broad scientific audience. Proteopedia http://www.proteopedia.org is an interactive, wiki web-resource whose pages have embedded three-dimensional structures surrounded by descriptive text containing hyperlinks that change the appearance (view, representations, colors, labels) of the adjacent three-dimensional structure to reflect the concept explained in the text.

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 [41]), which then loads with a slowly rotating crystal structure of hemoglobin in an interactive Jmol applet. (b) As the user reads that hemoglobin is a tetramer and that each of its subunits contains a heme prosthetic group, she or he can click on a green link in the corresponding text, eliciting a change in the hemoglobin in the Jmol applet, coloring each subunit a different color and displaying them in a smoothed trace of their α-carbon backbones, so that the hemes, colored in red, are easily visible. (c, d) While reading a sentence explaining that each heme contains an Fe²⁺ atom and clicking the appropriate green link, the user can watch the virtual hemoglobin molecule slowly rotate to a viewpoint that displays only a single heme, zoomed in, with its Fe²⁺ atom highlighted (c) or anchored to the protein (d). (e) When the user clicks on 'glutamic acid to a valine' he or she can see the specific point mutation in the hemoglobin molecule that causes sickle-cell anemia. Thus, text discussing and describing the structure and function is reinforced by immediate and specific three-dimensional visualization.

Figure 2

Automatically seeded pages for each of the over 50,000 entries in the PDB. (a) The Proteopedia page '2ac0' [42] contains the structure of a protein-DNA complex showing the structural basis of DNA recognition by P53 tetramers [43]. (b) The Proteopedia page '2bbn' [44] shows an ensemble of 21 NMR (nuclear magnetic resonance) models for the solution structure of a calmodulin-target peptide complex [45]. Note how the ensemble of the 21 NMR models reveals the more flexible portions of the protein structure. These are two examples (a, b) of automatically seeded pages created for PDB entries. The title sentence, in bold, comes from the title in the PDB file, and the "Published Abstract from PubMed" section text comes from the abstract of the article associated with the structure (retrieved from PubMed). A rotatable/zoomable three-dimensional structure in Jmol is displayed, and, under it, useful information about the structure including green scene links highlighting functional sites and ligands (as available in the PDB file), plus a link for further visual exploration in FirstGlance in Jmol, and links to related genes, domains, related PDB entries, structural annotation (InterPro, Pfam, UniProt, SCOP, CATH), functional annotation (GO and GeneCards), links to other resources, and links to download the coordinates of the structure. The side-by-side placement of the abstract and the three-dimensional structure is of immediate value, and these seeded pages also serve as strong starting points for addition of content. The amount of information available on each PDB entry varies, and thus so do the lengths of seeded pages.

Figure 3

An example of a protected page: a tutorial on Ramachandran plots. This image shows a section of a page containing a tutorial on Ramachandran plots. The green links in this section allow the user reading the page to compare the Ramachandran plots of three proteins with dissimilar structures by first viewing the three-dimensional structure of a particular protein and then viewing its Ramachandran plot. The plot displayed in the Jmol applet in the figure is that of acetylcholinesterase from PDB file 1eve. Points on the plot representing residues from α-helices are drawn in red, points representing residues from β-sheets are yellow, and points representing the other residues are in white. This page was authored by Professor Karl Oberholser, Department of Chemistry and Biochemistry, Messiah College, PA, USA. The page is titled "User:Karl_Oberholser/Ramachandran_Plots" (see [46]). "User:Karl_Oberholser" is Karl Oberholser's userpage, and this Ramachandran Plot page is a subpage of his userpage. All userpages and subpages thereof are editable only by their eponymous users. Since this Ramachandran plot page is a subpage of a userpage, it is editable only by Karl Oberholser, and is referred to as a protected page. He can count on this protected page in the wiki being unchanged, and use it as a three-dimensional "lecture slide". Since all user-added content in Proteopedia is released under the GNU FDL, other users may copy content from this page and add it to a publicly editable page, or another protected page, in Proteopedia with proper attribution to its author.