Eran Hodis

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

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. Proteopediahttp://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.

Overlapping codes within protein-coding sequences

Genomes encode multiple signals, raising the question of how these different codes are organized along the linear genome sequence. Within protein-coding regions, the redundancy of the genetic code can, in principle, allow for the overlapping encoding of signals in addition to the amino acid sequence, but it is not known to what extent genomes exploit this potential and, if so, for what purpose. Here, we systematically explore whether protein-coding regions accommodate overlapping codes, by comparing the number of occurrences of each possible short sequence within the protein-coding regions of over 700 species from viruses to plants, to the same number in randomizations that preserve amino acid sequence and codon bias. We find that coding regions across all phyla encode additional information, with bacteria carrying more information than eukaryotes. The detailed signals consist of both known and potentially novel codes, including position-dependent secondary RNA structure, bacteria-specific depletion of transcription and translation initiation signals, and eukaryote-specific enrichment of microRNA target sites. Our results suggest that genomes may have evolved to encode extensive overlapping information within protein-coding regions.

Proteopedia: A status report on the collaborative, 3D web-encyclopedia of proteins and other biomolecules

Proteopedia is a collaborative, 3D web-encyclopedia of protein, nucleic acid and other biomolecule structures. Created as a means for communicating biomolecule structures to a diverse scientific audience, Proteopedia (http://www.proteopedia.org) presents structural annotation in an intuitive, interactive format and allows members of the scientific community to easily contribute their own annotations. Here, we provide a status report on Proteopedia by describing advances in the web resource since its inception three and a half years ago, focusing on features of potential direct use to the scientific community. We discuss its progress as a collaborative 3D-encyclopedia of structures as well as its use as a complement to scientific publications and PowerPoint presentations. We also describe Proteopedias use for 3D visualization in structure-related pedagogy.

Proteopedia: A collaborative, virtual 3D web‐resource for protein and biomolecule structure and function

Received for publication, June 29, 2010Eran Hodis‡, Jaime Prilusky§, and Joel L. Sussman¶*From the ‡Department of Computer Science and Applied Mathematics, The Weizmann Institute of Science§Department of Biological Services, The Weizmann Institute of Science, ¶The Israel Structural ProteomicsCenter, Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100 IsraelProtein structures are hard to represent on paper. Theyare large, complex, and three-dimensional (3D)—four-dimensional if conformational changes count! Unlikemost of their substrates, which can easily be drawn outin full chemical formula, drawing every atom in a proteinwould usually be a mess. Simplifications like showingonly the surface of the protein or showing only a tracebetween its alpha carbons are preferred methods for rep-resenting the overall structure of a protein, and zoomed-in views showing all of the atoms in a certain part of theprotein can highlight important residues. Unfortunately,even these simplifications can look confusing when flat-tened into two-dimensional images as in printed text-books and scientific publications. Some aspects of therelationship between 3D protein structure and proteinfunction are more easily conveyed to students using 3Drepresentations of proteins, such as physical models orcomputer-generated molecular visualizations.Proteopedia (http:/www.proteopedia.org) is a new col-laborative web resource with pages describing protein,nucleic acid, and other biomolecule structures—includingcomplexes—in interactive, virtual 3D [1]. A typical pagein Proteopedia, which strives for encyclopedia-stylepages, shows a rotating 3D protein structure (using Jmol,[2]) adjacent to descriptive text containing hyperlinkscalled ‘‘scene links’’ that can be clicked to elicit a changein the 3D structure to illustrate a point made in the text.Proteopedia is a wiki, like Wikipedia, so every member ofthe scientific community with a user account can createand edit pages in the website, and its scene-authoringtools make it simple to add ‘‘scene links’’ to any page.To properly attribute both credit and responsibility topage-authors, the bottom of every page lists the usersthat have edited that page; each listed user name linksto a biographical account page describing the user’seducational and professional background to help thereader determine page reliability. There are more than200 user-added pages and more than 65,000 automati-cally generated ‘‘seeded’’ pages representing every entryin the Protein Data Bank (PDB), updated weekly.Educators have found Proteopedia to be a usefulteaching tool, and several instructors have adoptedProteopedia into their classrooms. The most obvious useis viewing existing user-added pages on molecules of in-terest (e.g. mechanosensitive channels [3] and HIV-1 pro-tease [4]). However, even if a specific protein lacks auser-added page in Proteopedia, if its structure has beensolved then the structure at least has an automaticallygenerated ‘‘seeded’’ page for its PDB entry with a rotata-ble 3D structure and useful information including theabstract from the publication describing the structure,automatically generated ‘‘scene links’’ for ligands in thestructure, and coloring by evolutionary conservation [5](e.g. luciferase, 2d1s [6]). Instructors have also createdpages as tutorials to either project in class or assign forstudents to read (e.g. tutorials on structural templates [7],serine proteases [8], and Ramachandran plots [9]). OnProteopedia, these instructor-created tutorials can beshared with other educators, who can adapt them foruse in their own classrooms, all while protecting the orig-inal tutorial from unwanted changes. Finally, several edu-cators have assigned class projects involving the crea-tion of Proteopedia pages on particular molecules ofinterest. The students learn through teaching, and theyend up contributing to a scientific and educationalresource (see undergraduate student-authored photosys-tem II page [10] and graduate student-authored triose-phosphate isomerase page [11]).BAMBED readers are invited to visit the Proteopediawebsite (http://www.proteopedia.org) and request a freeuser account.Beginning with this issue of BAMBED, selected Pro-teopedia pages that review a specific topic, protein, ormolecule and pass peer review will be published in a newsubsection of the feature Multimedia in Biochemistry andMolecular Biology Education. The Proteopedia page fea-tured in this issue of BAMBED also represents one of thewinning pages in the Proteopedia ‘‘Page of the Year Com-petition’’ for 2009 [12]. Thirty-one pages were entered intothe competition, which invited Proteopedia page-authors

An encyclopedic effort to make 3D structures easier to understand

For the first time in the short history of electronic publication, rotatable and zoomable 3D structures of biomolecules were integrated within the PDF file of the recent TiBS paper ‘Grasping molecular structures through publication-integrated 3D models’ by Kumar and Ziegler et al. [1]. This represents a major step forward in effective and simple communication of complex 3D data, one which has already been expanded into other spheres of science with the recent publication of a ‘3D PDF’ version of an astronomy paper in Nature [2].

Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters

Recent studies have shown a surprising phenomenon, whereby orthologous regulatory regions from different species drive similar expression levels despite being highly diverged in sequence. Here, we investigated this phenomenon by genomically integrating hundreds of ribosomal protein (RP) promoters from nine different yeast species into S. cerevisiae and accurately measuring their activity. We found that orthologous RP promoters have extreme expression conservation even across evolutionarily distinct yeast species. Notably, our measurements reveal two distinct mechanisms that underlie this conservation and which act in different regions of the promoter. In the core promoter region, we found compensatory changes, whereby effects of sequence variations in one part of the core promoter were reversed by variations in another part. In contrast, we observed robustness in Rap1 transcription factor binding sites, whereby significant sequence variations had little effect on promoter activity. Finally, cases in which orthologous promoter activities were not conserved could largely be explained by the sequence variation within the core promoter. Together, our results provide novel insights into the mechanisms by which expression is conserved throughout evolution across diverged promoter sequences.

Proteopedia: Exciting Advances in the 3D Encyclopedia of Biomolecular Structure

Proteopedia is a collaborative, 3D web-encyclopedia of protein, nucleic acid and other structures. Proteopedia (http://www.proteopedia.org) presents 3D biomolecule structures in a broadly accessible manner to a diverse scientific audience through easy-to-use molecular visualization tools integrated into a wiki environment that anyone with a user account can edit. We describe recent advances in the web resource in the areas of content and software. In terms of content, we describe a large growth in user-added content as well as improvements in automatically-generated content for all PDB entry pages in the resource. In terms of software, we describe new features ranging from the capability to create pages hidden from public view to the capability to export pages for offline viewing. New software features also include an improved file-handling system and availability of biological assemblies of protein structures alongside their asymmetric units.

TOOLS TO MAKE 3D STRUCTURAL DATA MORE COMPREHENSIBLE: EMOVIE & PROTEOPEDIA

To the crystallographer, solving a three-dimensional (3D) protein or molecular structure often times feels like the ultimate success, and surely it is. However, of utmost importance is the communication of the insights revealed by the 3D structure, especially those insights that relate structure to function. In order for these insights to reach their potential for guiding future research, they must reach biologists. The problem is that 3D structures are inherently complex and thus communicating insights about 3D structures to non-structural biologists can be difficult. To aid the structural biologist in this endeavor, we have created two useful tools. The first, eMovie, is a plug- in for PyMOL that makes creating macromolecular animations much more simple. The second, Proteopedia, is a community-annotated ‘wiki’ web- resource that links descriptive text to 3D views of structures, resulting in intuitive communication of structural information.