Download paper 5 - bio-ora article

Bio-Organic Reaction Animations
Steven A. Fleming, Department of Chemistry, Temple University, Philadelphia, PA 19122
URL http://bioora.ctlbyu.org/Bio ORA.zip
URL http://bioora.ctlbyu.org/html/Required Plugins/ViewPointMediaPlayerInstaller.pkg.dmg
The success of using animations to teach topics in the field of physics has been well
documented.i The use of animations in teaching chemistry has also been evaluated and the
evidence supports including animations of difficult 3D concepts in our courses.ii
Computer imaging technology is sufficiently advanced now to handle animations of the
actual molecules involved in the biochemical pathways. This type of multimedia presentation
can provide students with three-dimensional representations of the bio-molecules and threedimensional animations of binding and enzyme catalyzed reactions. This paper describes the
teaching tool Bio-Organic Reaction Animations (Bio-ORA) that we are developing. The
animations in Bio-ORA cover the chemistry of enzymes, carbohydrates, lipids, and nucleic acids.
Bio-ORA is a logical extension of the software Organic Reaction Animationsiii (ORA),
which provides a 3D image of over 50 organic reactions. ORA is packaged with the Maitland
Jones text Organic Chemistryiv and the software has been well received by the organic chemistry
community. It has been on the market for 10 years.
The enzyme portion of the Bio-ORA is our major focus. We have selected several
enzymes for inclusion in Bio-ORA. In order to be included in the program the mechanism of the
enzyme needs to be fairly well understood and a crystal structure of the enzyme or the enzymesubstrate complex needs to be available in the protein data bank. Having this information allows
us to animate from a known starting point. We have produced MM2 level calculations of the
mechanisms for 8 enzymes (acetylcholine esterase, chymotrypsin, citrate synthase, ribulose-1,5bisphosphate carboxylase oxidase, malate dehydrogenase, aminotransferase, cyclooxygenase,
and CDK2 kinase). Calculations have been performed using Spartan.v
This software runs on the common browsers (Explorer, Safari, and Firefox), although the
most recent version of Firefox (3.0) is not compatible at this point in time. Bio-ORA has two
screens for viewing each biomolecular process. The right hand screen is the initial pdb version of
the macromolecule. This view is provided by JMol software. Tabs on this half of the screen
allow the user to choose between the crystal structure, the text that corresponds to the animation
on the left screen, a 2D textbook version of the mechanism of the enzyme mediated reaction, and
a Flash clip that orients the crystal structure with the binding site that is shown on the left hand
screen. The user can manipulate the JMol view of the enzyme in the right hand screen. The left
hand screen has the animation of the calculated mechanism for the particular enzyme being
viewed. It is currently run using ViewPoint software. The animation initially shows a stripped
down view of the binding site. Substrates that are not already present in the pdb are then brought
into the animation. The chemistry that occurs in the binding site is animated and the metabolite is
shown departing the site.
There are several options for viewing the animation. There is a full play option that
shows a quick overview of the chemistry. A stepwise option allows the user to move slowly
through each step of the process. There are different speed options as well. A description of the
process on the right hand side of the screen automatically accompanies the animation and there is
an audio option. The user can listen to the text while watching the events unfold. Important parts
of the enzyme action (i.e. the amino acids involved in binding, co-enzymes, incoming substrates,
departing metabolites, necessary water molecules) are marked in the left-hand screen. The strings
connecting the marked parts can be deselected. The view of the animation in the left hand screen
can be manipulated by the user. A preferred view is programmed into the software so that the
best view can be easily found.
Bio-ORA also provides animations of other biomolecules. A carbohydrate chapter has the
small molecule process of converting the Fischer projection of glucose into glucopyranose. It
will also show a glycoprotein binding process. This will be designed to illustrate the significant
role that sugars play in binding at cell surfaces. A lipid chapter will be focus on phospholipids.
We will animate lipid bilayer formation on a small scale. We hope to incorporate a crystal
structure of a cell membrane or a similar lipid macromolecule. We are considering how to
animate movement of small molecules through the lipid layer. This will be the most challenging
calculation. We will show a better 3D image of the cell membrane forming event at a molecular
level than what is currently available. One advantage is that Bio-ORA will allow users to
manipulate the lipid animation. There is also a nucleic acid chapter of Bio-ORA. It currently has
an animation of intercalation of anthracene between two base pairs of a duplex. This chapter will
ultimately include a crystal structure of DNA on the JMol side and perhaps an animation of a
DNA-RNA binding event on the left hand side.
We have also been evaluating the software. This is a necessary process to ensure the
quality of the information that is being transferred. The assessment has been carried out in
collaboration with the Brigham Young University Center for Teaching and Learning (Larry
Seawright, PhD) and the Temple University Teaching and Learning Center (Baris Gundersel,
PhD). We have used results from student surveys to improve the product. For example, students
expressed a desire to see the book version of the enzyme-mediated reaction. This prompted us to
include the 2D version of the reaction into the right hand side of Bio-ORA. We have used exam
and quiz scores in an attempt to demonstrate the effectiveness of using animations to teach bioorganic chemistry. We don’t have sufficient data to make any conclusions in this area of the
assessment yet. We have used “think alouds” to modify the design of the software. The
assessment has been carried out at Brigham Young University, Southern Utah University,
Brigham Young University-Idaho, and Penn State-Harrisburg. Instructors from several other
universities have expressed an interest in the software and hopefully will join in the evaluation of
Bio-ORA in the near future.
In conclusion, we have developed software, called Bio-ORA, that can be used as a
teaching tool for bioorganic chemistry topics. In particular, we have animated enzymes,
carbohydrates, lipids, and nucleic acids. Bio-ORA can be used online via most browsers. Our
assessment of this product suggests that students benefit from the 3D exposure.
Acknowledgment. Bio-ORA has been supported by NSF (CCLI #0231421, #0717133
and #0935049), Brigham Young University, and Temple University. The animations are
produced by Rob Allen and Hardy Cherry at Brigham Young University’s Teaching and
Learning Center. Assistance from Ron Fleming, Gary Fredrickson, Ty Redd, and Paul Savage is
greatly appreciated.
“Impact of animation on assessment of conceptual understanding in physics,” Dancy, M. H.; Beichner, R. Phys.
Rev. ST Phys. Educ. Res. 2006, 2, 10104-1—10104-7.
ii
a) “Molecular Orbital Animations for Organic Chemistry.” Fleming, S. A.; Savage, P. B.; Hart, G. J. Chem. Educ.
2000, 77, 790-793. b) “Using Computer-Based Visualization Strategies to Improve Students' Understanding of
Molecular Polarity and Miscibility.” Sanger, M. J.; Badger, S. M., II. J. Chem. Educ. 2001, 78, 1412-1416. c) “The
Effects of a Two-Year Molecular Visualization Experience on Teachers' Attitudes, Content Knowledge, and Spatial
Ability” Williamson, V.M.; Jose, T.J. J. Chem. Educ. 2008, 85, 718-723.
iii
a) “Organic Reaction Animations. v2.2” Fleming, S. A.; Savage, P. B.; Hart, G. R. Brigham Young University
Creative Works, 2006. b) “Organic Reaction Animations. v2.3” Fleming, S. A.; Savage, P. B.; Hart, G. R. W.W.
Norton & Co., 2008.
iv
Maitland Jones, Jr. Organic Chemistry, 3rd Ed. W.W. Norton & Co. 2000.
v
Spartan is a product of Wavefunction, Inc.
i