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Dragging (and zooming and rotating) publication of 3D molecular structures into the 21st century

2008; Elsevier BV; Volume: 33; Issue: 9 Linguagem: Inglês

10.1016/j.tibs.2008.07.001

1362-4326

Jonathan K. Tyzack,

Hemoglobin structure and function

March 2008 represented the 50th anniversary of the publication of the first 3D structure of a protein determined by X-ray crystallography, that of myoglobin [1Kendrew J.C. et al.A three-dimensional model of the myoglobin molecule obtained by X-ray analysis.Nature. 1958; 181: 662-666Crossref PubMed Scopus (992) Google Scholar]. Since then, high-resolution 3D structures for a large and growing number of proteins (and other bio-molecules) have provided researchers with a visual grasp of their biochemical reactions of interest, thus, making them far easier to comprehend at a visceral and an intellectual level. However, the traditional 2D representations of 3D information that appear in print can only achieve so much and are, often, not as enlightening as they could, or should, be *This could be caused by limitations on the number of views that can be shown in a figure owing to space constraints imposed by the cost of publication, or even the complexity of the information itself (sometimes there is just too much to show and not enough ways to show it in a meaningful manner in a 2D format).*This could be caused by limitations on the number of views that can be shown in a figure owing to space constraints imposed by the cost of publication, or even the complexity of the information itself (sometimes there is just too much to show and not enough ways to show it in a meaningful manner in a 2D format).. Therefore, this outlet is at a disadvantage relative to the information that can be provided electronically, where full 3D imagery can be either obtained as original source files from databases such as the Protein Databank (PDB; http://www.rcsb.org/pdb/home/home.do) for use in specialist display software or converted into something more accessible to the layman, such as an electronic video format. However, both of these options also suffer from a serious limitation – they have to be supplied as supplementary material to the article rather than being integrated within it and both require the use of more software to look at their content, in addition to that of the ubiquitous portable document format (PDF) viewers used by readers across the globe to access articles. In an ideal world, these extra downloads and additional software requirements would not be necessary and the information would be available to the reader as part of the original article. In their Opinion article in this September 2008 issue of TiBS, Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] describe how it is now technically possible to include 3D imagery within a PDF. This means that it is possible to access the 3D structure(s) while reading the article, all as part of a single download (Box 1). Crucially, it also permits the reader to manipulate the display of the 3D image, which enables them to observe the structure(s) from any perspective rather than being limited to the restricted views provided by the authors in their figures or movies. The software enables different display options to be toggled on and off so that, for example, parts of the structure(s) can be hidden or shown at will (Box 2 and Box 3), in addition to dragging, zooming and rotating. The malleability of this display enables the reader to get a much better perspective of the information the structure(s) can provide, thus, greatly increasing the educational value of the article. Although this will hardly be news to structural biologists who are used to achieving the same effects (and more) using their specialist modelling software or to researchers familiar with viewing videos of structures online, it does make life considerably easier for the reader to gain access to this information via a single download. Likewise, it means an author can potentially show something to the reader that might have been very difficult to convey using a 2D image.Box 1Current restrictions on the distribution of the new PDF formatBecause it is necessary for librarians to be able to archive electronic articles in a format that is guaranteed to be accessible in the future, publishers such as Elsevier must provide them in ‘standard’ formats. At the time of writing, owing to the newness of the embedding of 3D imagery or Flash formats into a PDF, the resultant files are currently ‘non-standard’ and, therefore, Elsevier cannot offer as a primary download the version of the PDF in which the 3D imagery is embedded. Instead, TiBS is offering the Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] article in full – including the embedded, fully interactive 3D figure – as a supplemental download from ScienceDirect (http://www.sciencedirect.com/science/journal/09680004). In the future, it is hoped that this new PDF format will also become a recognized standard and the current need to offer it as a separate download will become moot.Box 2A quick ‘how-to’ for 3D figures embedded in PDFsViewing of the interactive 3D display in the (supplemental PDF version of) Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] requires the use of version 7.1 or higher of Adobe Reader (or Acrobat) on either the Macintosh, Linux or Windows platforms †The file generated is a ‘version 1.6’ PDF from version 8 of the software and a ‘version 1.7’ PDF from version 9. For other PDF viewers, there is a differing degree of information displayed when the article is viewed. For example, only the 2D figure image will be visible if version 6 of Adobe Reader is used and, at the time of writing, Preview in Mac OS X is unable to display either the 2D image or the 3D image.†The file generated is a ‘version 1.6’ PDF from version 8 of the software and a ‘version 1.7’ PDF from version 9. For other PDF viewers, there is a differing degree of information displayed when the article is viewed. For example, only the 2D figure image will be visible if version 6 of Adobe Reader is used and, at the time of writing, Preview in Mac OS X is unable to display either the 2D image or the 3D image.. However, the use of version 8 or higher (Box 3) is recommended owing to better compatibility with the new features of the PDF format. To access the 3D image, click the static 2D figure image (Figure Ia in the supplemental PDF version of Ref. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar]) that is present for the benefit of those who do not have a latter-day version of Adobe Reader installed (and also for those using the print copy of the article). Once clicked, the 2D image converts to a display of the 3D structure (Figure Ib). By default, a toolbar is present in the top left corner (not shown here), the display of which is toggled on and off by clicking the triangle below it. By clicking on the ‘Model Tree’ icon to the right of the ‘Views’ drop-down menu in this toolbar, a pane opens in the sidebar showing a list of the content in the model [Figure Ib(i)] and, also, a list of the predefined views that the authors have provided as starting points for the readers [Figure Ib(ii)]; some of which are equivalent to the static images in the 2D figure. These views are also accessible in the ‘Views’ drop-down menu. With the 3D view active, the buttons in the toolbar can be used to change the action that occurs when manipulating the structure with the mouse pointer (i.e. rotation, dragging or zooming); alternatively, keyboard modifiers such as the control, shift or command keys can be used to achieve the same effects. By toggling on and off the differing elements in the list of content in the sidebar, the surfaces of the molecules can be hidden or displayed, for example (compare Figure Ib with Figure Id). Entire molecules can similarly be hidden to leave the desired view of the content, such as the ligands or individual subunits – this will be particularly helpful to the reader when comparison of two different structures, such as the apo- and ligand-bound forms of a protein, is necessary.The transparency of the surfaces and the background colour used in the display can also be manipulated. However, owing to the original purpose of the Adobe software, some of the available options are more suited to CAD and CAM than the display of molecular structures and their usefulness is limited here (as is the case for many of the lighting options). Conversely, some options typical of other 3D software for molecular structures are not available at present (e.g. rainbow colourations of individual proteins or helices and β sheets). Hopefully, the ability to control which of these options is shown, together with the addition of those options currently lacking, will be included in future versions of the Adobe software. To exit from the 3D display, a right click on the image brings up a contextual menu with the option to disable the 3D display and return to the 2D images (Figure Ic).Box 3Adobe Acrobat 9 and Adobe Reader 9During the course of the production of the Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] article, Adobe released new versions of their Acrobat and Reader software, bringing them to version 9.0. The result is a few changes to the process used by the authors in the creation of the embedded 3D imagery in their PDF, as indicated in the ‘Note added in proof’ to their article. Although time has precluded them from testing the new software thoroughly and updating their article correspondingly ‡However, the authors have prepared a basic step-by-step guide showing how to generate a 3D figure in the Adobe software, which is available for download as supplementary material to their article.‡However, the authors have prepared a basic step-by-step guide showing how to generate a 3D figure in the Adobe software, which is available for download as supplementary material to their article., the most important difference is that Adobe Acrobat 3D Toolkit has been discontinued and the functionality made a part of the Adobe 3D Reviewer software of the Adobe Acrobat 9.0 Professional Extended package. It does not seem to be the case that the feature set for the 3D display of Adobe Reader 9 has been altered to any great extent, although there are a few additional buttons in the toolbar. However, it is worth mentioning that, in addition to permitting the embedding of 3D imagery, version 9.0 also makes it possible to embed Flash content into a PDF. This means that other content, such as time-lapse photography generated of fluorescently labelled proteins in a cell, for example, can be included within the download of an article. Thus, the potential usefulness of these features of the new PDF format in the life sciences has expanded beyond that of structural biochemists and into the realm of cell biologists and others. Because it is necessary for librarians to be able to archive electronic articles in a format that is guaranteed to be accessible in the future, publishers such as Elsevier must provide them in ‘standard’ formats. At the time of writing, owing to the newness of the embedding of 3D imagery or Flash formats into a PDF, the resultant files are currently ‘non-standard’ and, therefore, Elsevier cannot offer as a primary download the version of the PDF in which the 3D imagery is embedded. Instead, TiBS is offering the Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] article in full – including the embedded, fully interactive 3D figure – as a supplemental download from ScienceDirect (http://www.sciencedirect.com/science/journal/09680004). In the future, it is hoped that this new PDF format will also become a recognized standard and the current need to offer it as a separate download will become moot. Viewing of the interactive 3D display in the (supplemental PDF version of) Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] requires the use of version 7.1 or higher of Adobe Reader (or Acrobat) on either the Macintosh, Linux or Windows platforms †The file generated is a ‘version 1.6’ PDF from version 8 of the software and a ‘version 1.7’ PDF from version 9. For other PDF viewers, there is a differing degree of information displayed when the article is viewed. For example, only the 2D figure image will be visible if version 6 of Adobe Reader is used and, at the time of writing, Preview in Mac OS X is unable to display either the 2D image or the 3D image.†The file generated is a ‘version 1.6’ PDF from version 8 of the software and a ‘version 1.7’ PDF from version 9. For other PDF viewers, there is a differing degree of information displayed when the article is viewed. For example, only the 2D figure image will be visible if version 6 of Adobe Reader is used and, at the time of writing, Preview in Mac OS X is unable to display either the 2D image or the 3D image.. However, the use of version 8 or higher (Box 3) is recommended owing to better compatibility with the new features of the PDF format. To access the 3D image, click the static 2D figure image (Figure Ia in the supplemental PDF version of Ref. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar]) that is present for the benefit of those who do not have a latter-day version of Adobe Reader installed (and also for those using the print copy of the article). Once clicked, the 2D image converts to a display of the 3D structure (Figure Ib). By default, a toolbar is present in the top left corner (not shown here), the display of which is toggled on and off by clicking the triangle below it. By clicking on the ‘Model Tree’ icon to the right of the ‘Views’ drop-down menu in this toolbar, a pane opens in the sidebar showing a list of the content in the model [Figure Ib(i)] and, also, a list of the predefined views that the authors have provided as starting points for the readers [Figure Ib(ii)]; some of which are equivalent to the static images in the 2D figure. These views are also accessible in the ‘Views’ drop-down menu. With the 3D view active, the buttons in the toolbar can be used to change the action that occurs when manipulating the structure with the mouse pointer (i.e. rotation, dragging or zooming); alternatively, keyboard modifiers such as the control, shift or command keys can be used to achieve the same effects. By toggling on and off the differing elements in the list of content in the sidebar, the surfaces of the molecules can be hidden or displayed, for example (compare Figure Ib with Figure Id). Entire molecules can similarly be hidden to leave the desired view of the content, such as the ligands or individual subunits – this will be particularly helpful to the reader when comparison of two different structures, such as the apo- and ligand-bound forms of a protein, is necessary. The transparency of the surfaces and the background colour used in the display can also be manipulated. However, owing to the original purpose of the Adobe software, some of the available options are more suited to CAD and CAM than the display of molecular structures and their usefulness is limited here (as is the case for many of the lighting options). Conversely, some options typical of other 3D software for molecular structures are not available at present (e.g. rainbow colourations of individual proteins or helices and β sheets). Hopefully, the ability to control which of these options is shown, together with the addition of those options currently lacking, will be included in future versions of the Adobe software. To exit from the 3D display, a right click on the image brings up a contextual menu with the option to disable the 3D display and return to the 2D images (Figure Ic). During the course of the production of the Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] article, Adobe released new versions of their Acrobat and Reader software, bringing them to version 9.0. The result is a few changes to the process used by the authors in the creation of the embedded 3D imagery in their PDF, as indicated in the ‘Note added in proof’ to their article. Although time has precluded them from testing the new software thoroughly and updating their article correspondingly ‡However, the authors have prepared a basic step-by-step guide showing how to generate a 3D figure in the Adobe software, which is available for download as supplementary material to their article.‡However, the authors have prepared a basic step-by-step guide showing how to generate a 3D figure in the Adobe software, which is available for download as supplementary material to their article., the most important difference is that Adobe Acrobat 3D Toolkit has been discontinued and the functionality made a part of the Adobe 3D Reviewer software of the Adobe Acrobat 9.0 Professional Extended package. It does not seem to be the case that the feature set for the 3D display of Adobe Reader 9 has been altered to any great extent, although there are a few additional buttons in the toolbar. However, it is worth mentioning that, in addition to permitting the embedding of 3D imagery, version 9.0 also makes it possible to embed Flash content into a PDF. This means that other content, such as time-lapse photography generated of fluorescently labelled proteins in a cell, for example, can be included within the download of an article. Thus, the potential usefulness of these features of the new PDF format in the life sciences has expanded beyond that of structural biochemists and into the realm of cell biologists and others. Unfortunately, as Kumar et al. [2Kumar P. et al.Grasping molecular structures through publication-integrated 3D models.Trends Biochem. Sci. 2008; 33: 408-412Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] describe, at this time there are real and potential limitations to the technology in both developing and displaying the images. The software used to create the PDF has been targeted at the computer-aided design (CAD) and modelling (CAM) sector for creating models of buildings or commercial products, and not at researchers of the life sciences. However, it is our hope that (once these limitations are overcome) this format will become the norm for article distribution in the future rather than remaining an occasional oddity, especially for a journal such as TiBS, where provision of clear and meaningful content to educate our readers is of primary concern. Given that the PDF format was first put to widespread use in academic publishing, perhaps what is most surprising about the development of what now seems to me to be an obvious feature, is that it has taken so long.