In the Classroom
Use of Molecular Models for Active Learning in Biochemistry Lecture Courses James H. Hageman Department of Chemistry, University of Colorado, Denver, Colorado 80217-3364
[email protected] The historical development, intellectual underpinnings, and construction and use of physical molecular models for both research and teaching are wonderfully described in three articles (1-3). Del Re pointed out (2) that “physical models are tools of descriptive analogical thinking” and perhaps, not surprisingly, became an important part of the conceptual framework of chemistry by the 1920s (3). Physical models provide a way of gaining a three-dimensional image of a material world that is on the scale of the wavelength of light, and as Francoeur notes (1), “The idea of manipulation is central to the process of mechanical molecular modeling.” Models of various sorts have been developed over the decades, from wire frameworks to the space-filling CPK models, and quite a few have been offered commercially (1); heuristically, they each have advantages and disadvantages and have been criticized for both their intellectual and physical limitations (1, 4, 5). Gupta and Parkash (4) provided a good survey of the earlier literature describing the use of models in the teaching of chemistry, particularly as cited in this Journal. They also describe the alternative to the use of commercial molecular models or kits, the construction of in-house general-purpose models for teaching. This Journal has continued to stress the importance of models, both physical and computational models, for the teaching of chemistry and biochemistry through the monthly “JCE Featured Molecules” section, such as a recent one on antioxidants (6). In using molecular models for teaching biochemistry, an instructor is confronted with the complexity of structure presented by macromolecules as well as interactions between small molecules and macromolecules and between different chemical classes of macromolecules. A multi-institutional study of seven different learning tools employed in teaching introductory biochemistry found that students rated the molecular models as the most valuable of the tools (7). The participants in this study developed a novel, rapid-prototyping construction of physical models from RasMol computer images; students who took part in three-week laboratories with hands-on manipulations of models evinced an increased interest in the subject and asked more sophisticated questions than was the usual case (7). These unique physical models have been adapted for use in lower-level classes and are reported to enhance learning (8). The Center for BioMolecular Modeling will loan these unique physical models to other institutions (7, 8). Recently, a simple aluminum foil template in combination with three-dimensional physical molecular models has been reported to be an effective way to teach the concepts of drug binding to their intended targets (9). Considerable evidence, as cited above and elsewhere, demonstrates that construction and manipulation of physical molecular
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Figure 1. Comparison of β-D-glucose with Maruzen (left) and Darling molecular models (right). The one-inch grids and ruler reveal the 5-fold difference in relative size of molecular models.
Figure 2. Maruzen model of a trisaccharide fragment of cellulose in plastic bag as presented for grading.
models by students is a useful tool for grasping concepts in chemistry and biochemistry. In spite of this, my informal observations are that for the most part faculty members tend to “recommend” that students purchase and use models or use models as demonstration tools in classroom presentations or in lab exercises. Over a 15 year period, I developed an active-learning strategy to engage students in the regular use of models that built their interest in molecular aspects of biochemistry. Briefly, each student was required to buy a biochemistry kit, to build models on regular basis to bring to class, to use the models with classmates to answer strategic questions related to the molecules, and to build additional structures from these molecules and turn in the built models for grading. Molecular Models and Active-Learning Strategies Two framework model kits, the Maruzen 5000-Bio-Organic kit and the Darling Customized New Mexico State University Biochemistry kit, have been used successfully (Figure 1). Each has its advantages and disadvantages that are outlined briefly in Table 1. Each student was required to buy one type of kit in a given
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In the Classroom Table 1. Advantages and Disadvantages of the Two Molecular Models Kits Darling Kit Pros
Cons
Larger size (1 Å = 5 cm) makes building easier and some features clearer Greater complexity of models requires more time to learn to construct molecules Double bonds lock into place and peptide bonds are fixed
Larger size makes carrying constructed models and grading more difficult
Unshared electron pairs can be readily shown in the model, allowing hydrogen bonds to be shown even for water
Larger size results in too great a flexibility in construction of macromolecular structures
Less expensive for students to buy Supplier will customize kits Maruzen Kit Pros
Cons
Smaller size (1 Å = 1 cm) allows even largest models to fit in a clear, ziplock bag, making carrying and grading easier
Smaller size leads to lost parts and causes trouble for manipulation by some students
Putting atoms together is intuitive
Repeated use causes some noticeable wear in parts; joints become loose, double bonds rotate
Stiffness of joints is just right for holding a desired structural conformation More expensive for comparable number of parts Assembly of atoms is easier and faster
Table 2. Examples of Models To Be Built Before Class and Strategic Questioning and Manipulations of Molecular Models in Class Model To Build before Class Methane with an H-bonded water clatherate around it
Questions Posed in Class
Activity or Activities To Be Done in Class
Are these highly stable species kinetically or rapidly changing? What might be different about the H-bonded structure you have made if the molecule being surrounded with waters were ionic?
Is your clatherate the same as your neighbors'? Is that okay? With two neighbors show the orientation of a few waters for a central ammonium ion. Show how the orientations of the waters would change if the central ion were a chloride ion. Turn in any clatherate model for grading.
Alanine (do not specify At pH 7, which groups have charges? Are your charges stereochemistry to students) the same as your neighbors' models? Is your model superimposable on your neighbors' models? Which stereoisomer did you build, D or L?
Fix your model as necessary so that it is the correct ionic species and the L isomer then place it in your ziplock bag to turn in.
The dipeptide L-spartyl-Lphenylalanine, showing the correct charged form at pH 7
Build the ionic form at pH 1.0. With one of your neighbors, join your models to make the tetrapeptide (DFDF) and turn this in for grading.
Are any of the atoms coplanar? Which ones? Why are they coplanar? Which is the amino end and which is the carboxyl end? What is the methyl ester of the phenylalanine named?
An L-alanine octapeptide with Identify the amino end and the carboxyl end of the peptide. What is the net charge on this peptide at all L-alanines in their fully extended conformations pH 7? What would you predict its solubility to be in water? Why? Which atoms are coplanar in the fully extended state? An R helix from the (L-ala)8 peptide, with all H-bonds in place
Is the turn of your helix the same as those of your Pack your helix with that of one or more of your neighbors neighbors' models (i.e., right handed)? How would in a way that might be a stable conformation. In what biological structures does this sort of packing occur? you describe this structure? Where are the side chains positioned? In a space-filling model is there a cavity in What forces might contribute to this stability? What the center of the helix? effect would charged side chains have on packing? Turn in your model of an R helix for grading.
semester. Because of the relative costs, I shifted to using the Darling kits in spite of some disadvantages. Students were told what molecular model to build in the period before it was due and to place it in a clear, one- or two-gallon ziplock bag, having her or his name and the name of the compound at the top of the bag, and to bring it to class. Once the models were used in the class, the students placed the ziplock bags (Figure 2) in a large cardboard box or large plastic trash bag. The number of students in class varied 292
Bend the backbone wherever you can. Which atoms remain coplanar? About which backbone atoms can rotation occur? Are all possible rotations possible? If not, why not? What are the limitations? Take your model home in preparation for the next class.
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from 40 to 80. Models were graded as follows: 3, totally correct (the vast majority of models); 2, minor errors; 1 major errors; 0, not turned in on time. Grading never required more than about 15-20 min. Typically, 10% of the grade for the class was allotted to the model building work. Initially, I found that just having students build and turn in models for grading increased their engagement and that grading their constructed models eliminated nearly all complaints about
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In the Classroom
the cost of the models. Over time, I found that having students answer strategic questions about their models, modifying their models, and sharing their knowledge with each other for brief periods in class greatly increased their understanding of key features of biomolecular structures and their functional roles in cells. Table 2 provides some examples selected to cover a typical introductory biochemistry course and questioning strategies developed and used to enhance the learning experience. (An expanded version of Table 2 is available in the supporting material.) Discussion Anecdotally, students repeatedly commented in their course evaluation forms on the high value of the models as part of their learning in the course. The sense of accomplishments students had was evident from their discussions with each other. Furthermore, considerable pride was shown by team members, for example, when they were stopped on campus by their friends and asked what a model of coenzyme A or DNA double helix was. After a number of years of using these models as described, the prices for the kits rose appreciably in one year, and I decided they were too expensive to require students to purchase them. However, over the next two years, I noticed such a decline in the quality of written answers on exams concerning structure and function of biomolecules that I reinstated the model building strategy. I continued and expanded the use of models for the remainder of my teaching career. In a narrower application, Beltramini et al. documented that students gained enhanced understanding of structure-function relations when they used three-dimensional models of DNA and RNA (10) as part of their instructional methods. Unfortunately, over the many years in which the strategy described here was used, no rigorous, systematic, and controlled assessment of its effectiveness was carried out. Indeed, the extensive methodological detail provided here is offered in part with the hope that others may be encouraged to carry out a formal assessment of the approach. In any case, based on the documented studies cited above and my repeated qualitative observations, I am confident that when rigorously tested in controlled studies, these active-learning strategies developed with molecular models are likely to prove pedagogically beneficial. Finally, two unintended consequences of using the models as described were also observed and were likely to have contributed to
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increased learning. I repeatedly noticed that the in-class and outof-class building and reasoning tasks led to both strong collaborations among students solving certain problems and also to the emergence of peer leaders to deal with more complex building projects. These peer leaders in effect became the teachers in constructing and analyzing the more complex biomolecules. Not only is collaborative learning a well-established useful learning process (11), but peer-led team teaching has been shown to have dramatic impacts on student persistence in the teaching of organic chemistry (12). The latter suggest that introducing an intentional peer-led strategy in the use of these models might offer even grater benefits than those observed. Acknowledgment The work of Jennifer Kirschke in the preparation of the photographs is gratefully acknowledged, as are the years of support of students and faculty members in the Department of Chemistry and Biochemistry at New Mexico State University. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
11. 12.
Francoeur, E. Soc. Stud. Sci. 1997, 27, 7–40. Del Re, G. Hyle 2000, 6, 5–15. Francoeur, E. Hyle 2000, 6, 63–84. Gupta, H. O.; Parkash, B. J. Chem. Educ. 1999, 76, 204–205. Lipkowitz, K. J. Chem. Educ. 1984, 61, 1051–1052. Coleman, W. F. J. Chem. Educ. 2008, 85, 464. Roberts, J. R.; Hagedorn, E.; Dillenburg, P.; Patrick, M.; Herman, T. Biochem. Molec. Biol. Educ. 2005, 33, 105–110. Bain, G. A.; Yi, J.; Beikmohamadi, M.; Herman, T. M.; Patrick, M. A. J. Chem. Educ. 2006, 83, 1322–1324. Geldenhuys, W. J.; Hayes, M.; Van der Schyf, C. J.; Allen, D. D.; Malan, S. F. J. Chem. Educ. 2007, 84, 979–982. Beltramini, L. M.; Araujo, A. P. U.; de Oliveira, T. H. G.; dos Santos Abel, L. D.; da Silva, A. R.; dos Santos, N. F. Biochem. Molec. Biol. Educ. 2006, 34, 187–193. Cooper, M. M.; Cox, C. T., Jr.; Nammouz, M.; Case, E.; Stevens, R. J. Chem. Educ. 2008, 85, 866–872. Wamser, C. C. J. Chem. Educ. 2006, 83, 1562–1566.
Supporting Information Available Expanded version of Table 2. This material is available via the Internet at http://pubs.acs.org.
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