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DAGS95: Electronic Publishing and the Information Superhighway
May 30--June 2, 1995
Boston, Massachusetts

Electronic Publishing of Virus Structures in Novel, Multimedia Formats on the World Wide Web

Stephan M. Spencer: ~~Institute for Molecular Virology and Integrated Microscopy Resource,~~; ~~University of Wisconsin-Madison~~; ~~627 Bock Laboratories~~; ~~1525 Linden Drive~~; ~~Madison, WI 53706~~; ~~608-263-6288~~; ~~sspencer@rhino.bocklabs.wisc.edu~~; ~~http://www.bocklabs.wisc.edu/sspencer.html~~; Current link: http://www.stephanspencer.com/
Jean-Yves Sgro: Institute for Molecular Virology,; University of Wisconsin-Madison; 735 Bock Laboratories; 1525 Linden Drive; Madison, WI 53706; 608-262-7464; ~~sgro@rhino.bocklabs.wisc.edu~~; ~~http://www.bocklabs.wisc.edu/sgro.html~~; Current email: jsgro@wisc.edu; Current: http://www.virology.wisc.edu/virusworld/jys.php

Abstract

Visualizations of complex biological structures such as viruses are well-suited to distribution via the electronic medium of the World Wide Web, complementing the peer-reviewed publication of figures in scientific papers. Animation and color can be employed to accentuate particular features of structure, and thus a greater information content can be imparted than would be possible with printed media. Structural information that is easily accessible in a standard, meaningful, and even interactive format can be an effective tool in teaching and research. We at the Institute for Molecular Virology, University of Wisconsin-Madison have developed a World Wide Web server (~~http://www.bocklabs.wisc.edu/Welcome.html~~) (http://www.virology.wisc.edu/virusworld) * which disseminates structural information in novel formats world-wide to scientists, teachers, students, and the public.

Animations, interactive models, and high resolution color-coded images of viral particles and proteins are available, many of them exclusively, from our site. To create comparable visualizations using generally available resources would prove difficult, to a large extent because of the complexity of these structures which would require specialized computing equipment, a great deal of computing expertise, and datasets that are either not publicly available or that need to be reconstructed by symmetry operations from the PDB coordinates (which represent one sixtieth of the complete particle). The previously rendered images and animations, however, can be readily downloaded and viewed on personal computers connected to the Web.

We have used animation and false color extensively to present structural details that may not have been visible without additional figures, such as orthogonal or radial sections, multiple views, or stereoscopic images. Coloring the virus particle according to the protein subunits (Fig. 1a) allows the viewer to determine the composition of notable structural elements on the particle surface. Radial depth cueing [1] (Fig. 1b) is a technique for applying false color that correlates with the radial distance from the center of the particle. We often use these coloring techniques in conjunction with animation techniques. Both spin animation, i.e. rotation of the particle around an axis (Fig. 2a), and radial depth cueing are effective in enhancing the surface topography and improving the presentation of peaks, canyons, and pores. The cropping of frontal (Fig. 2b) or radial (Fig. 2c) sections reveals internal features.

FIGURE 1: Two types of false color are applied to virus structures. a.) Color corresponds to the protein subunit. Human rhinovirus 14 (a common cold virus) [6]; VP1 (Viral Protein 1) is colored blue, VP2 green, and VP3 red (VP4 is inside and not visible). Rendered using srf [7] on a Silicon Graphics workstation. b.) Color is a function of the distance from the center of the particle, i.e. radial depth cueing [1]. Flock house virus (an insect virus) [8]. Rendered using Spline [9] and MIDAS-Plus [10] on a Silicon Graphics [11] workstation.

FIGURE 2: Three types of animation were used to display the virus structures. The core particle of mammalian reovirus [12], shown with radial depth cueing. a.) Rotation around an axis (spin animation). b.) Cropping in the z- direction. c.) Radial cropping. Rendered using Iris Explorer [13] on a Silicon Graphics workstation.

We offer yet another useful representation of virus crystal structure data, one that takes advantage of the capability of the WWW protocol to ÒviewÓ atomic coordinate files interactively [2]: a three-dimensional model of an icosahedral asymmetric unit of the virus, displayed in the context of the icosahedral framework (Fig. 3). These interactive models employ the KineMAGE [3] molecular graphics program as a helper application that needs to be installed on the user's computer. We also anticipate offering "navigable" QuickTime [4] movies of rendered virus structures in the near future, which will provide even greater flexibility by alleviating the requirement of a molecular graphics helper program, yet still allowing the real-time manipulation of these structures in three dimensions.

This type of electronic publishing has marked advantages over a CD-ROM because it can be updated instantly. Unlike a CD-ROM, performance is affected by Internet bandwith limitations, namely the type of connection and overall Internet traffic. Once the animation or structural file has been transferred, however, all manipulation becomes local to the user's machine, and thus these visualizations truly offer real-time interactivity.

FIGURE 3: The icosahedral asymmetric unit of human rhinovirus 14, viewed interactively on a Macintosh [4] using the molecular graphics program KineMAGE [3]. a.) Normal view. b.) Stereo view.

These virus visualizations enhance conventional virology instruction by offering unique resources to students and teachers. Animated or interactive visualizations of viruses allow students to interact in new ways with the course material and can supplement traditional teaching aids such as textbooks and lectures. With advances like the World Wide Web protocol and Kinemage, electronic publishing of virus structures have become decreasingly less platform-dependent and thus the are now accessible to a much wider audience. In addition to these visualizations, we provide other course materials on our server, such as virology tutorials, course notes, syllabi, and journal articles. This material is most effectively assembled into a coherent whole by the teachers who are on the 'front lines,' not by us as electronic publishers. To achieve this end, we have designed a fill-in form interface that allows instructors without any knowledge of HTML (HyperText Markup Language) [11] to create clickable course outlines ("hypersyllabi") which are maintained on our server. This coupled approach of providing useful information in unique, multimedia formats and a dynamic environment for organizing the information will, we believe, enhance distance education and collaborative teaching.

Acknowledgments

We gratefully acknowledge Jack E. Johnson and colleagues at the Structural Biology Group at Purdue University for supplying us with the atomic coordinates that were used to generate Figure 1b and Timothy S. Baker and colleagues also at Purdue University for supplying us with the three-dimensional cryo-electron microscopy dataset that was used to generate Figure 2.

This work was performed at the Institute for Molecular Virology, University of Wisconsin-Madison, with partial funding provided by the Lucille P. Markey Charitable Trust. Work in establishing the WWW Server for Virology was used to fulfill part of the requirements for awarding the Masters of Science degree in Biochemistry (5-95) to S.M.S. for work he performed in the laboratory of Prof. Max L. Nibert.

References

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[13]: Iris Explorer. Silicon Graphics, Inc., Mountain View, CA