RasMol and Mage in the Undergraduate Biochemistry Curriculum

RasMol and Mage in the Undergraduate Biochemistry Curriculum. Steven W. Weiner, Paul F. Cerpovicz, ... Keywords (Feature):. Teaching with Technology ...
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Teaching with Technology

James P. Birk Arizona State University Tempe, AZ 85287

RasMol and Mage in the Undergraduate Biochemistry Curriculum Steven W. Weiner,* Paul F. Cerpovicz, Dabney W. Dixon, Donald B. Harden, Donna S. Hobbs, and Donna L. Gosnell Department of Chemistry, Physics, and Engineering Studies, Armstrong Atlantic State University, 11935 Abercorn Extension, Savannah, GA 31419-1997; *[email protected]

With the availability of high-quality graphics for the personal computer, there is a trend for college chemistry teachers to use computer-generated 3-dimensional molecular models to illustrate chemical properties and reactivity. The use of models for visualization of chemical concepts is linked to greater achievement in freshman chemistry (1). Students in freshman chemistry who viewed computer animations depicting the particulate nature of matter demonstrated a higher conceptual understanding of chemical phenomena than students who viewed textbook or chalkboard figures (2). High school students who have used hand-held or computergenerated 3-dimensional molecular models to learn about organic chemical structures scored significantly higher on isomeric identification tests than students who used 2-dimensional representations of the same molecule (3). At Dickinson College, organic chemistry students use a computer molecular modeling program to visualize the 3-dimensional structures of organic molecules and predict their regiochemistry and relative reactivity, and predictions based on the computer modeling exercises are confirmed by laboratory experiments (4 ). While the visualization of 3-dimensional molecular models leads to greater understanding of chemical concepts discussed in freshman and organic chemistry, it is also very important that students visualize the 3-dimensional structure of proteins, cofactors, and nucleic acids in order to understand biochemistry because there is a very close relationship between the structure of a biomolecule and its function. While students can build physical models of small molecules discussed in freshman chemistry and organic chemistry, building physical models is impractical for proteins and nucleic acids that contain hundreds or thousands of atoms. A convenient way to view the structure of proteins and nucleic acids is through the use of computer programs that generate accurate 3-dimensional images of large molecules that can be rotated and manipulated. A number of commercially available programs have been developed for this purpose, but they may be prohibitively expensive for many college programs. Two very powerful programs, Mage and RasMol, can be downloaded from the Internet and distributed freely, and they enable one to view and manipulate computer-generated 3-dimensional images of biomolecules very easily. As part of a Connecting Teachers and Technology Course Development Grant funded by the Board of Regents of the University System of Georgia, we were charged with enhancing the undergraduate Biochemistry I and II curricula through the extensive use of RasMol and Mage. Some of the activities and the innovative educational materials we developed and

an assessment of these programs from both the teachers’ and students’ perspectives are discussed in this paper. Available Freeware and Data Files RasMol (Raster Molecules) is a visualization program written by Roger Sayle while he was a graduate student in the Computer Science Department at the University of Edinburgh. Glaxo Research & Development later employed Sayle to continue developing RasMol. RasMol can translate a structure file in pdb (Protein Data Bank) format from the x, y, z- coordinates of each atom, based on X-ray crystallography and nuclear magnetic resonance studies, into a 3-dimensional image that can be manipulated. The program, which is available for Windows, MacOS, and UNIX platforms, is free and in the public domain. RasMol can be downloaded from the RasMol home page on the World Wide Web (http:// www.umass.edu/microbio/rasmol ) (5, 6 ). An enhanced version of RasMol for pedagogical use is available from the Modular Chemistry Consortium project at the University of California, Berkeley (http://www.umass.edu/microbio/rasmol/getras.htm). Literally thousands of pdb files of proteins and nucleic acids may be downloaded from the Brookhaven Protein Data Bank Web site (http://www.rcsb.org/pdb/). A convenient way to search for pdb files of proteins and nucleic acids of interest is through the Molecules R Us Web site at the National Institutes of Health (http://molbio.info.nih.gov/cgi-bin/pdb) (5, 6 ). Simply type in the keywords of the structure of interest, and the search engine will find all the pdb files that match. The highlighted list of pdb files includes the Brookhaven Protein Data Bank four-character code and a one-sentence description of the file. Clicking on the desired highlighted entry gives the viewer the option of saving the pdb file in text format to the hard drive of the computer. The structure can be viewed in 3-dimensional space by opening the pdb file within the RasMol program, or it can be viewed directly over the Internet by configuring the Web browser to launch RasMol as a “helper application” (5). Mage is a program written by Robert M. Weiss, David Richardson, and Jane Richardson of Duke University (7). It translates structural files called kinemages into 3-dimensional images. The program, available for Windows, MacOS, and UNIX platforms, is free and in the public domain. Both Mage and the kinemages can be downloaded from the Journal of Protein Science home page (http://www.prosci.org). The kinemages are indexed according to protein type, which makes searching for the appropriate structures relatively easy.

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By selecting the appropriate highlighted kinemage file from the index, one is given the option of saving the kinemage to the hard drive of the computer and opening it within the Mage program. Alternatively, the kinemages can be viewed directly over the Web by configuring the Web browser to launch Mage as a “helper application”. Using Rasmol and Mage to Teach the Structure– Function Relationship in Hemoglobin With RasMol, the viewer can rotate the image in 3dimensional space and selectively change the color, shape, and size of different portions of a complex molecule such as a protein or a nucleic acid. One can change the scale of the image to get a total view of the molecule to or focus in on a particular region of the molecule, such as the active site of an enzyme or the binding site of a protein to DNA. Manipulations of images through RasMol are achieved through a combination of preset menu options and a series of commands that the viewer can type at a RasMol Command Line that interfaces with the graphics window. One of the standard topics covered in the undergraduate biochemistry course is the structure–function relationship of hemoglobin. A useful way to teach this topic as a lecture– demonstration is with a laptop computer connected to a LCD projector to project the image on a large screen. Through a series of menu-driven options and specific commands entered at the RasMol Command Line, one can transform the default 3-dimensional image of deoxyhemoglobin, where all atoms are represented in a wire-frame mode colored in the CPK color scheme (Fig. 1), into the manipulated image (Fig. 2). By starting with the default image, the student may not be able to see the structurally important features of the protein; but using RasMol, the instructor can carry out a series of manipulations of the default image to selectively highlight features of deoxyhemoglobin as a basis for the discussion of the structure–function relationship of the protein. Students can see how the four subunits of hemoglobin comprise mainly α-helices, that each subunit has a flat porphyrin ring, and that an iron atom fits in the cavity of the porphyrin ring while also being coordinated to a specific histidine residue. Mage differs from RasMol in that each of the pdb structures has been manipulated (using the Prekin program) by the author of the file to illustrate specific scientific points. The text accompanying the file can be very useful. However, because many authors make files, there is a lack of uniformity that some students find confusing. The text associated with a kinemage can be very detailed or very sparse. Many kinemages include an option to animate between structures (7). On one kinemage of human hemoglobin, the viewer can animate between the oxy and deoxy forms of the molecule. By animating between the oxy and deoxy form, the viewer sees how the tetramer is rotated approximately 15° about a vertical axis through the dimer–dimer interface. Through a close-up view of the alpha-beta interface, one can see deoxyhemoglobin and the network of hydrogen bonds and salt bridge interactions that stabilize it, and then animate to the oxy form to show the absence of these hydrogen bonds and salt bridges. A close-up view of the heme pocket in the deoxyhemoglobin reveals that the iron atom is puckered slightly out of the plane of the porphyrin ring. By animating 402

Figure 1. Human deoxyhemoglobin, Brookhaven Protein Data Bank Classification Code, 1HGA.pdb.

Figure 2. Human deoxyhemoglobin, Brookhaven Protein Data Bank Classification Code, 1HGA.pdb (GIF export). The structure is displayed in a RIBBONS mode and colored according to CHAIN. There are four chains, colored dark blue, light blue, green, and yellow. One heme group is associated with each chain. The porphyrin ring is colored white and displayed in the STICKS mode. The iron atom is colored purple and displayed in the SPACEFILL mode. Histidine residues colored red and displayed in the STICKS mode are coordinated to the iron atoms.

between the deoxy form and the oxy form, one can see how the iron atom shrinks in size upon binding oxygen. As a result, the iron atom moves from outside the plane of the porphyrin ring to just inside the porphyrin ring, causing the movement of the histidine residue covalently attached to the iron (8). Hence, with Mage the instructor can use an animated 3dimensional model to demonstrate how the binding of oxygen to hemoglobin induces the conformational change from the deoxy to the oxy form of the protein. From a teacher’s perspective, doing a computerized lecture–demonstration with Mage on protein structure and function, nucleic acids, or detailed views of the active sites of enzymes may not require much preparation time. In a kinemage, there are a series of preset views with accompanying text that explains the important features. Many kinemages are self-explanatory, and both the instructor and the student can use the accompanying text in conjunction with the customized menu of image manipulations to discuss the structure and function of important biomolecules. While the

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Table 1. Responses to Selected Sur vey Questions Survey Question

Response

Did seeing 3-D structures of proteins help you understand biochemistry?

81% agreed or strongly agreed, only 2% strongly disagreed

Did seeing 3-D structures of RNA and DNA help you understand biochemistry?

81% agreed or strongly agreed

Did seeing 3-D structures of cofactors help you understand biochemistry?

76% agreed or strongly agreed

Did seeing 3-D structures of amino acids, sugars, and 82% agreed or strongly agreed nucleotides help you understand biochemistry? In your opinion, is Mage or RasMol the more effective teaching tool?

RasMol (43%), Mage (47%), both are equal (10%)

In your opinion, did Mage or RasMol have a greater impact on your understanding of biochemistry?

RasMol (55%), Mage (38%), both are equal (6%)

graphics from Mage are not as sharp as in RasMol, one can superimpose or animate between several structures at once with Mage. With RasMol, the user has a greater number of options for manipulating the 3-dimensional images but can look at only one structure at a time. As many as six structures can be viewed simultaneously with the Berkeley enhanced version of RasMol. Using RasMol, the instructor must have a knowledge of the structurally important features of the protein or nucleic acid in order to generate a powerful image that is pedagogically useful and may have to rehearse the presentation, deciding which combination of typed commands and menu-driven options best illustrates the structure–function relationship of a biomolecule. One can make the analogy between a biochemistry teacher using RasMol and an art historian interpreting a painting. Art historians use their knowledge of art and of the artist to interpret the significance of the painting. Instructors use their knowledge of the structure–function relationship of a biomolecule and select the proper set of commands in RasMol to explain the significance of the 3-dimensional image generated. Students’ Assessment of Rasmol and Mage as Teaching Tools The features of RasMol and Mage have been discussed in previous literature (5–7, 9). This article emphasizes teaching activities using RasMol and Mage, students’ assessment of the relative merit of these programs, and students’ perceptions of the effectiveness of the programs as teaching tools. For this assessment, a uniform, two-part survey was distributed to all students enrolled in either Biochemistry I or Biochemistry II between the summer quarter of 1997 and spring quarter of 1998. A total of 80 students from Armstrong Atlantic State University, Augusta State University, Georgia Southern University, Georgia State University, and Valdosta State University were surveyed. There were 13 questions for students to answer on a scale of 1 (definitely no) to 5 (definitely yes), and a series of short-answer questions. All of us used either Mage or RasMol or both for lecture–demonstrations. Some of us also developed specific exercises or teaching materials using RasMol and Mage outside of lecture and appended questions pertaining to these activities to the survey. Selected survey results are summarized in Table 1. Students were asked to list the topics in Biochemistry I or Biochemistry II where Mage and RasMol were most helpful.

The most frequent responses dealt with protein structure and function, the interactions between an enzyme and substrate, cofactor, or inhibitor, and the study of DNA. To quote some of the students directly, RasMol and Mage are most helpful for learning protein structure and primary, secondary, and tertiary structure of proteins. One student replied, “It was most helpful in understanding the structure and function of the active sites of different proteins and how binding the substrate produces a conformational change.” Furthermore, “The protein chemistry, especially the nature of an active site was a lot more understandable.” Using Mage and RasMol was very helpful “in understanding the interaction between cofactors and substrates and inhibitors and substrates, [and] also being able to visualize various H-bonds and other covalent bonds in the RNA and DNA molecule.” The Relative Merits of Rasmol and Mage from the Students’ Perspective A student’s perception of a teaching and learning tool can be very different from that of an educator. For example, the instructor may think that a certain book has wonderful examples of elegant syntheses in organic chemistry. If the student is unable to follow the explanations because of the way the book is written, or if the mechanism diagrams are not clear, then the book will not be an effective teaching and learning tool for that student. An overwhelming majority of the students surveyed perceived Mage and RasMol as very helpful in their understanding of biochemistry. However, the students were divided about which program was the more effective (see Table 1). While a slight majority of students thought that RasMol had the greater impact on their understanding of biochemistry, a slight majority of also perceived Mage to be the more effective teaching tool. To help us understand these responses, students were asked to report what they liked the most and the least about RasMol and Mage. There was a remarkable similarity in the responses. The majority of students cited the quality of the graphics and the options available in RasMol to allow for various manipulations of the images. To quote one student, RasMol had “the best images and manipulation of images…and more ways to look at them.” Another student said, “I like the wide variety of functions and features that it is able to perform.” Yet another responded, “You can highlight what you want, or change the color of what you want.” Other students concurred, “It’s very versatile, you can create

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an infinite number of structures from one file, each stressing a particular part/concept.” When asked what they liked least about RasMol, the majority of the students responded that there was no text to accompany the images. Although one can create RasMol scripts to include text captions, these students did not use any RasMol scripts. Describing RasMol itself, one student said, “It does not provide you with information about the structure you are viewing.” More than one student complained that RasMol did “not have a description readily available of the structure” and that there was “no information describing what we are supposed to see.” Some students complained that some of the commands for manipulating images were difficult and that learning the program was somewhat complicated. Also, there was no easily accessible directory of commands. As one student replied, “The commands were often difficult to understand at first, [and] the instructions for the program were often difficult to understand also.” When asked what they liked most about Mage and the kinemages downloaded from the Protein Science home page, the majority of students cited the accompanying text and captions. Many also cited the ease of operation of the program. To quote one student, Mage offers “a lot of information with structures, and [is] very easy to use.” Students also liked the different preset views of proteins and the animation features. In particular, they found the preset views very helpful for “its ability to show how an inhibitor interacts with the active site of a particular protein.” One student praised Mage for allowing the viewer to be “able to see the side chains [of a protein] clearly.” Another said his favorite aspect of Mage was “being able to see the structures in three dimensions and the interactions between molecules.” When asked what they liked least about Mage, the majority stated that the graphics are not as sharp as those available from RasMol. They also mentioned the lack of choices to manipulate the images except for the fixed options associated with a given kinemage. As one student observed, “It doesn’t allow you to select any specific part of a protein and make it stand out from the rest of the protein like RasMol allows you to do.” Student Use of Rasmol and Mage outside the Classroom Since RasMol, Mage, the pdb files, and the kinemage files are free and can be downloaded from the Internet, many students used these programs outside of class time either on campus or at home. The majority (76%) responded that they used these programs on campus outside of class time. For the minority of students (24%) who said they did not use the programs outside of class, most (54%) said that they were “too busy”. Some students (21%) said “space was not available at a convenient time in the University computer lab”; others (15%) responded that they were “not interested”. Only 36% of the students reported that they have used Mage and RasMol at least somewhat at home. The primary reason cited by students for not using these programs was that they “did not have a computer” (53%). Other students said that they were “too busy” (31%), and only a small percentage of students cited a “lack of interest” (10%) or that the programs were “too difficult to use” (6%) as a reason for not using the programs at home.

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Teaching and Learning Activities with Rasmol and Mage All of us have used either RasMol or Mage or a combination of both programs for demonstrations in lecture. At Valdosta State University, Donna Gosnell uses RasMol when lecturing on the levels of protein structure and specifically for myoglobin and hemoglobin. She also has used the DNA and lipid membrane tutorials downloaded from the RasMol home page at the University of Massachusetts (http://www. umass.edu/microbio/rasmol). As an out-of-class exercise, students are required to find pdb files for protein structures on the Web, view them with RasMol, and write summaries about their structure. Packaged with the Biochemistry text by Horton et al. (10) is a disk with the software Exploring Molecular Structure, v. 2.0, developed by Kim Gernert at Duke University. The software package, which is available in MacOS and Windows versions, contains a collection of Mage-based exercises. Students are required to choose two exercises and complete them at home or on the chemistry department computers. After providing them with some basic instructions for the operation of RasMol, Gosnell encourages students to download the RasMol manual from the RasMol home page and experiment further with the program on their own. At Georgia Southern University, Paul Cerpovicz uses a desktop computer connected to an LCD projector to show structures of proteins and nucleic acids with RasMol. He finds RasMol an ideal tool for viewing the different conformations of DNA and how they interact with proteins. For example, when discussing B-DNA, RasMol may be used to highlight specific residues and binding sites in the major or minor groove of the molecule. The program allows one to clearly highlight the N-6, N-7, and O-6 atoms of the purines and the N-4 and O-4 pyrimidine atoms to show how they are located in the major groove and available for hydrogen bonding to amino acid residues of DNA-binding proteins. In addition to classroom activities, each student is given a floppy disk containing RasMol and selected pdb files, and a guide sheet for how to use the program and download images from online databases. Students use these resources as both a study aid for understanding molecular structure and to prepare class presentations on selected proteins, nucleic acids, or protein– nucleic acid complexes. At Augusta State University, Donna Hobbs uses both Mage and RasMol during her lectures on protein structure and function. Students use Mage to look extensively at secondary structure. Several good kinemages have been developed to show α -helices, β-sheets, and the many interactions that stabilize them. For examples of tertiary and quaternary structure, Hobbs’s class uses both RasMol and Mage. While Hobbs agrees with her students that Mage is much easier to use, she says, “RasMol sure is prettier! Sometimes Mage can be frustrating, because you want to change a picture but you can’t.” Students spend one week in lab working with Mage and another week working with RasMol. For learning how to use Mage, they are given a set of kinemages to view and a series of questions about these files. They must read the text accompanying the image and identify particular amino acids, and measure distances between certain residues. They are given a set of directions to help them learn RasMol commands and a series of questions that they can answer. The capstone for Biochemistry I is a team presentation and paper about a

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protein of their choice. Using either RasMol or Mage, they must discuss the structure and function of the molecule and how the structure is related to the function. While some of the preparation for this team exercise can be done during the two 3-hour lab periods where students learn how to use Mage and RasMol, most of the preparation is done outside of class. At Armstrong Atlantic State University the biochemistry sequence is taught in the chemistry and engineering computer lab. When the instructor is carrying out a demonstration with RasMol or Mage using a laptop and an LCD projector to project the image on a screen, students are seated at computer terminals following the demonstration, carrying out the same manipulations as the instructor. When using RasMol, students are encouraged to write down the series of commands used to generate the images that illustrate key features of protein structure and function. This allows students to reexamine the structures on their own outside of class in a pedagogically useful way. Weiner uses RasMol to manipulate the structures of triosephosphate isomerase and hemoglobin to illustrate the concepts of protein structure hierarchy. He uses Mage to teach about the mechanism of catalysis of serine proteases. By using Mage to superimpose the two protein structures, students learn that chymotrypsin and trypsin are structurally very similar. That chymotrypsin and trypsin have the same catalytic triad but different substrate specificities can be demonstrated by animating between views of the active sites of these proteins. During the first lab meeting for the course, the instructor leads a hands-on workshop on using RasMol and Mage and downloading structure files from the Internet. So that they can use these programs outside of class, each student receives a copy of RasMol, Mage, selected pdb files, selected kinemages, and a guide sheet summarizing what is covered in the workshop. Biochemistry Students Peer Teach Using Rasmol and Mage Students in Biochemistry I at Armstrong Atlantic State University are required to give a short multimedia presentation, using either Mage or RasMol with a laptop and LCD projector, on the structure and function of a protein of interest. The protein must be one that is not discussed specifically during lecture, and students must download the appropriate pdb files or kinemages from the Internet. Students are asked to point out features of the overall tertiary and quaternary structure of the protein, describe any cofactors required for activity, and highlight catalytically important residues. They are also required to talk about the reaction catalyzed by the protein and the mechanism of catalysis, if known. While some students may obtain some of the required information directly from the kinemages or pdb files, additional information is obtained from various undergraduate-level biochemistry texts and graduate level monographs that the instructor puts on reserve in the library. Some students obtain information about their protein from the primary literature after doing a computerized literature search. In addition to learning more about a protein of interest, students became comfortable using RasMol and Mage, learn how to search Internet databases and download files, and gain experience speaking in public doing a multimedia presentation. From the survey data obtained from Weiner’s classes, the overwhelming majority of students felt that the exercise was an

extremely positive experience. When asked whether this presentation exercise helped them understand protein structure and function, 11 of 13 students strongly agreed that it did. The majority of students surveyed also felt that this exercise definitely made them feel more comfortable using computers. An almost identical pattern of response can be seen when students were asked whether this presentation exercise helped them become more comfortable with searching Internet databases and downloading files. The majority of students strongly believed that the exercise helped them become more comfortable with searching the Internet and downloading files. The two students who chose not to rate the previous question with a numerical response stated that they had plenty of previous experience with searching Internet databases and downloading files. Students were asked to list two positive aspects of the presentation exercise. Many students appreciated the practical experience of speaking in public and giving a multimedia presentation. To quote one student, “Presentations allow several good exercises including preparation and research, writing and especially speaking. Making a presentation using multimedia techniques puts to rest the mystery of using computers for this exercise.” Students frequently said that learning more about proteins that interest them is one of the positive aspects of the presentation exercise. To quote another student, “[The presentation exercise] gives an opportunity for public speaking and allows for research on a protein that interests the student.” Students were also asked to list two negative aspects of the presentation exercise. Surprisingly, the majority, 7 of 13, replied that were no negative aspects. The next most frequent response to this question dealt with the amount of time required for the exercise. Some students (3 of 13) thought that the exercise required too much time for them to prepare adequately and there was not enough time to present their research on the protein. To alleviate the time constraints associated with learning the programs and preparing for the presentation exercise, a portion of the laboratory time is now allocated for students to learn how to use RasMol and Mage and to prepare for and deliver their multimedia presentations. Additional Learning Resources Using Rasmol Dabney Dixon, Donald Harden, and Zhihong Ye of Georgia State University, in collaboration with Luis Arias of the Inter American University of Puerto Rico, have developed a series of visualization curricula for biochemistry, organic chemistry, and general chemistry using RasMol. The GLACTONE Project is an initiative funded by the Chancellor of the University System of Georgia to provide support to institutions within the system for instructional technology in chemistry. Dixon and Harden maintain the GLACTONE Web site, http://chemistry.gsu.edu/glactone. This site contains a series of static images of the proteins associated with glycolysis and the Krebs cycle, of vitamins bound to proteins, and of small organic molecules associated with various flavors and fragrances. These images are GIF exports of images generated with RasMol. If the Web browser is properly configured, these structures can be viewed in 3 dimensions with RasMol upon double-clicking the static images. The structures were either

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downloaded from the Brookhaven Protein Data Bank or created with a 3-dimensional molecular modeling program that can save the output in a pdb format. More recently, the team at Georgia State University and the Inter American University of Puerto Rico has developed a CD-ROM with a more extensive compilation of pdb files of proteins, nucleic acids, vitamins, sugars, amino acids, small organic molecules, and small inorganic molecules. The CD contains a copy of RasMol and the complete operation manual for the program. By clicking on the highlighted name of the pdb file, one is able to view and manipulate the 3-dimensional image of that molecule with RasMol. At Georgia State University, this CD has been used in Organic Chemistry, Biochemistry I and II, and a special topics graduate course on protein structure and folding. A copy of the CD has been distributed to each of the institutions involved in the GLACTONE project. At Georgia Southern University, Paul Cerpovicz and Brenda Wojciechowski have written RasMol scripts with CHIME to create a Web-based general chemistry module (http://www2.gasou.edu/chemdept/general/molecule) where students learn about the characteristic geometry of classic small inorganic structures by looking at dynamic 3-dimensional images of these molecules. CHIME, a plug-in for the Netscape Web browser created by MDL Information Systems, Inc., enables one to view RasMol scripts directly over the Web. CHIME can be downloaded for free from the Internet (http://www.mdli.com/ download/chimedown.html), and instructions for its use in biochemistry are available at (http://www.umass.edu/microbio/ chime/index.html). Rasmol in High Schools and Two-Year Colleges While infusing RasMol and Mage into the undergraduate biochemistry curriculum was our primary objective, a second goal was to spark chemistry and biology students’ interest in science by letting them view and manipulate 3-dimensional images of molecules that are familiar daily life. The majority of students in the undergraduate biochemistry courses felt strongly that RasMol would be useful in freshman chemistry (64%) and in high school (72%) as well. During the past two years, we have traveled to high schools and two-year colleges throughout Georgia to give a series of hands-on workshops for high school teachers and college faculty on how to operate RasMol. The workshop participants were shown examples of molecules that would be relevant to the courses they taught. At some of the workshops, participants were shown how to search for and download pdb files from the Brookhaven Protein Data Bank. Each participant received a floppy disk containing RasMol and selected pdb files. At some of the workshops at the two-year colleges, faculty brought their students to participate. An example of where RasMol would be appropriate in the introductory courses is the teaching of chirality. The instructor can use RasMol to view the structures of the 20 naturally occurring amino acids in proteins. By rotating the image in 3-dimensional space, the students can translate a flat Fischer projection of an L-amino acid into a 3-dimensional molecule with a tetrahedral chiral center. By rotating the 3-dimensional image of the chiral molecule one can obtain a view of the chiral center, which makes it very easy to assign the absolute configuration of the molecule. Other applications include showing the double 406

helix of DNA and highlighting the G–C and A–T base pairs as well as the sugar–phosphate backbone. Conclusion The initiatives using RasMol and Mage to enhance the undergraduate biochemistry curriculum have been very successful from the perspective of both teachers and students. The wider application of these programs in lower-level undergraduate courses and high schools has been successful as well. The programs are relatively easy to learn and a significant percentage of students are using them for independent study either at school or at home. When it comes to the value of these freeware programs, one may find exception to the old adage “You get what you pay for.” Acknowledgments Funding for the activities described in this paper was provided by the following grants: 1. University System of Georgia Board of Regents Connecting Teachers and Technology Grant, “Visualization of Biomolecules in Biochemistry with RasMol”. Dabney W. Dixon and Donald B. Harden, Georgia State University, 1996. 2. University System of Georgia Board of Regents Teaching and Learning Grant, “Visualizing Biomolecules with RasMol”, Dabney W. Dixon and Donald B. Harden, Georgia State University, 1997. 3. GLACTONE Project, Office of the Chancellor of University System of Georgia, Dabney W. Dixon, Georgia State University, 1995–1998. 4. Georgia Statewide Academic and Medical System (GSAMS) grant, “Visualizing Structures of Biomolecules”, Dabney W. Dixon and Donald B. Harden, Georgia State University, 1996.

Literature Cited 1. Talley, L. H. J. Res. Sci. Teach. 1973, 10, 263. 2. Williamson, V. M.; Abraham, M. R. J. Res. Sci. Educ. 1995, 32, 521. 3. Copolo, C. F.; Hounshell, P. B. J. Sci. Educ. Technol. 1995, 4, 295. 4. Crouch, R. D.; Holden, M. S.; Samet, C. J. Chem. Educ. 1996, 73, 916. 5. Horton, R. M. BioTechniques 1997, 22, 660. 6. Millar, N. School Sci. Rev. 1996, 78, 55. 7. Richardson, D. C.; Richardson, J. S. Prot. Sci. 1992, 1, 3. 8. Voet, D.; Voet, J. In Biochemistry, 2nd ed.; Wiley: New York, 1995; pp 228–232. Also see mb_hb.kin, from the floppy disk of kinemages that accompanies this text. The coordinates for human deoxy and oxy hemoglobin in the kinemage mb_hb.kin are from the respective pdb files, Brookhaven Protein Data Bank classification codes 2HHB and 1HHO. 9. Sayle, R. A.; Milner-White, E. J. Trends Biochem. Sci. 1995, 20, 374. 10. Horton, H. R.; Moran, L. A.; Ochs, R. S.; Rawn, J. D.; Scrimgeour, K. G. Principles of Biochemistry, 2nd ed.; Prentice Hall: Upper Saddle River, NJ, 1996.

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