Teaching molecular 3‐D literacy

An understanding of three-dimensional structure/function relationships is increasingly important to modern biochemistry and molecular biology. Not only are the overall “folds” that illuminate evolutionary relationships uncompromisingly three-dimensional but so, too, are the critical details at active sites. Fortunately, most protein and nucleic acid structures are now readily available on the Internet from the Protein Data Bank [1, 2], as are good tools for displaying them on small computers such as Mage [3, 4], Rasmol [5, 6], Chime [7], and SwissPDBViewer [8, 9]. However, teaching these skills and concepts effectively is nevertheless a challenge, because the prior education of students has concentrated entirely on one-dimensional (verbal) and two-dimensional (static pictures) information; many students feel unfamiliar and uncomfortable with 3-D materials. Many biochemistry textbooks now come with supplements using molecular graphics, such as Voet et al. [10], Branden and Tooze [11], and Horton et al. [12]. There are web sites with teaching materials on protein structure, such as Eric Martz’s Chime and Protein Explorer site [7], the Protein Society’s ProTeach site [30], Robert Bateman’s undergraduate kinemage site [31], our own Kinemage Homepage [4], and a site planned for this journal. There have also been papers reporting on teaching use of these molecular graphics tools in a variety of settings and approaches [13–16]. So far, however, there is little experimental data on either the absolute or the relative effectiveness of these materials for teaching 3-D literacy and only minimal guidance about the best ways to use them in the classroom. We do not yet have hard quantitative data on effectiveness, although we are now working on that problem under a joint National Science Foundation grant with Robert Bateman. However, for many years we have been using molecular graphics in our classes and striving to improve the 3-D literacy of our students and colleagues. We have learned a number of things that don’t work and some that do, and we would like to share those lessons with other biochemical educators. In the 1970s we learned to make “worm” drawings of protein backbones on the blackboard, but we taught mainly from hard copy handouts of text and 2-D figures. Our first experience developing systematic teaching materials to illustrate molecular structure was over 20 years ago, when J.S.R. worked out conventions for hand-drawn ribbon schematics such as Fig. 1, aiming to do as well as possible at translating the 3-D organization of protein “folds” into a static 2-D form on paper [17, 18]. Descendents of those representations, now rotatable in three dimensions, are a standard feature of current molecular graphics. We still give our classes a set of full-page line drawings as a “coloring book” and have them hand back a few pages colored in some way that makes sense in three dimensions. Except for an occasional M.D./Ph.D. student who feels insulted by this assignment, everyone else enjoys it very much; their results are often very inventive and/or esthetic. The active involvement in decoding the 2-D picture helps them connect printed figures with their computer exercises and also helps them recognize the handedness of structural features. Soon after the ribbon schematics, our research laboratory obtained an Evans & Sutherland PS300 graphics machine, and D.C.R. wrote a display program (Chaos) for it. We then developed an extensive series of laboratory exercises with that system for the graduate students in our advanced seminar course. This was very effective but only workable for a dozen students at a time. In the 1980s we also made several movies and a large number of slides for use in introductory classes. Movies can communicate very well for a specific example, but we never had very many, because making good ones was very difficult, they could not be modified to suit new needs, and they inherently lacked the ability of interactive graphics to zoom in and show the answer to a student question. The use of actual physical models is also an effective learning tool, but they are more expensive and require more teacher interaction than computer graphics, and they work well only for small scale pieces of structure. We still use both brass Kendrew stick models and plastic “CPK” space-filling models in our seminar class to build initial familiarity with the geometry and motions of small atomic groupings up to a few residues. In 1989, with the help of a North Carolina Biotechnology grant, we first got a computer projector that could show interactive molecular graphics to a large group in the classroom. It was a big, expensive machine, with a special fast phosphor to allow stereo; it required a fussy alignment and convergence procedure, and we had to wheel an ‡ To whom correspondence should be addressed. Tel.: 919684-6010; Fax: 919-684-8885; E-mail: jsr@kinemage.biochem. duke.edu. 1 The abbreviations used are: 3-D, three dimensional; 2-D, two dimensional. © 2002 by The International Union of Biochemistry and Molecular Biology BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Printed in U.S.A. Vol. 30, No. 1, pp. 21–26, 2002