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Q 2010 by The International Union of Biochemistry and Molecular Biology
BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION
Vol. 38, No. 6, pp. 359–364, 2010
Article
Beyond Textbook Illustrations: Hand-held Models of Ordered
DNA and Protein Structures as 3D Supplements to Enhance
Student Learning of Helical Biopolymers
Received for publication, April 9, 2010, and in revised form, May 11, 2010
Karnyupha Jittivadhna, Pintip Ruenwongsa, and Bhinyo Panijpan‡
From the Institute for Innovative Learning, Mahidol University, 999 Phuttamonthon 4 Road,
Salaya, Nakhon Pathom 73170, Thailand
Textbook illustrations of 3D biopolymers on printed paper, regardless of how detailed and colorful, suffer
from its two-dimensionality. For beginners, computer screen display of skeletal models of biopolymers
and their animation usually does not provide the at-a-glance 3D perception and details, which can be
done by good hand-held models. Here, we report a study on how our students learned more from using
our ordered DNA and protein models assembled from colored computer-printouts on transparency film
sheets that have useful structural details. Our models (reported in BAMBED 2009), having certain distinguished features, helped our students to grasp various aspects of these biopolymers that they usually
find difficult. Quantitative and qualitative learning data from this study are reported.
Keywords: Helical structure, DNA, polypeptide, science education.
Helical structures of biopolymers are ordered and have
symmetry in three dimensions. College students have to
learn about helices of the double-stranded DNA, the
single-stranded protein a-helix, and possibly others in
bioscience classes. Even high school students studying
biology are exposed to these common helical structures
and are examined for their knowledge of these structures. However, when asked to draw a sketch of the
DNA double helix with as little details as that drawn by
Francis Crick’s wife, Odile, for the seminal Nature paper
in 1953 [1], quite a few students, including some graduates, cannot do it well: no clear helical (right-handed)
sense, haphazard hydrogen bondings between basepairs, no major and minor grooves, the strands are not
antiparallel, and so forth. Students do not perform much
better with the bare-backbone polypeptide a-helix: no
clear helical (right-handed) sense, haphazard hydrogen
bondings, each amino acid residue is not quite correct.
Given these difficulties in student learning this aspect
of chemical biology, researchers recommended enhancing the learning of DNA and protein structures through
the use of three-dimensional physical models [2–4]. Herman et al. [5] and Bain [6] reported that concrete visual
models that can be easily manipulated, play an important
role in capturing the interest of students at both high
school and undergraduate levels and encouraging more
‡ To whom correspondence should be addressed. Tel.: þ66 (0)
2441-9020; Fax: þ66 (0) 2441-0479. E-mail: [email protected].
This work is supported by Tertiary Education Commission,
Ministry of Education.
This paper is available on line at http://www.bambed.org
sophisticated thinking about the tangible molecular
world.
It should be noted that one obvious limitation to the
widespread use of physical models is their high cost and
limited availability. To provide our students with an easy
access to a useful learning tool, we had developed physical models of ordered structures of the B-form DNA,
protein a-helix, and b-pleated sheet made from computer-printed transparency film cut-outs. We used the
already-assembled DNA double helix with two central
axes (made from straight wires) [7] to teach students,
medical as well as graduate bioscience, to learn the
essential structural details of DNA and their role when
interacting with drugs and proteins using the hydrogen
bond donor and acceptor groups on the bases and the
electrostatic charge on the phosphate group. The relative
spacings of the major and minor grooves change with
the tilting of the base pairs from B to A form and from
right-handed to the left-handed conformation, simply by
manipulating the two central axes, illustrate their conformational change without breaking any covalent bond.
Because the printed base pairs are transparent, the
stacking of successive base pairs and their relative twist
(of the stacking) can be seen and measured. Our polypeptide a-helix and b-pleated sheet (parallel, antiparallel)
with connecting polypeptide turns (having only alanine
side chains for simplicity) show their regular backbone
and regular side chain arrangement, a feature students
usually miss. The instruction for building these parsimoniously designed models is described in a recent article in
this journal [7]. The model enables the instructor to
simplify, illustrate, and explore these chemical features
359
DOI 10.1002/bmb.20427
360
BAMBED, Vol. 38, No. 6, pp. 359–364, 2010
as they are made to scale and provide atomic details
with the conventional CPK color scheme.
The aims of this study: (1) to identify the areas where
students have difficulties in understanding these biologically important helical structures they are exposed to
only as illustrations in textbooks and (2) to assess the
contribution of our models to students’ understanding of
ordered DNA and protein structures and their functions.
All these were based on both quantitative and qualitative
data from educational studies.
STUDY DESIGN AND METHODS
Because the polypeptide chain, the protein a-helix and
b-sheet, the polynucleotide chain, and the B-form DNA
are common biochemical structures taught in nearly
every introductory biology courses, we were thus able to
conduct this educational study at multiple sites and with
students of various academic backgrounds. The study
was done during the year 2006–2009 with 498 student
volunteers: 9th–12th graders (aged 14–19) in high
schools, freshmen and sophomores, and preclinical
medical students (aged 17–20), who had previously been
exposed only to textbook presentations of DNA and
protein structures during their earlier school/academic
years.
Three instruments were used in this study: a multiplechoice content questionnaire, an open-ended content
questionnaire, and another open-ended questionnaire,
which was used for group interviews. All questions were
specifically developed for this study.
The multiple-choice and open-ended content questionnaires were administered as the pretest (before modelhandling activity but with easy access to textbooks) and
posttest (during the model-handling activity), both containing the same questions. The students received the
open-ended written questionnaire after they handed in
their responses to the multiple-choice questionnaire. The
group interviews were conducted at the end of the
activity session.
The multiple-choice questionnaire, which included nine
questions, was filled out by all the 498 students. These
were questions on base pairing, hydrogen bond donoracceptor possibility of each of the bases, polynucleotide
strand polarity, general equivalence of both ends of the
double helix, location of grooves with respect to the
base pairs and the backbones, configuration of the peptide bond, number of hydrogen bonds in an a-helix
spanning 12 amino acid residues, the 21 helicity of the bpleated sheet, and the possibility of the reverse turn in
the sheet. Each student answered the questions individually, but they were allowed to discuss the material as
groups of four to six. During the pretest, students were
also allowed to consult the textbooks provided for them.
The posttest survey was carried out while the students
were handling the models to exploit the latter’s educational potential. Students in each group were allowed to
manipulate the complete set of models and some components, especially the base pairs of the DNA modeling
kit, and participated in reasoned discussions about some
structural features of the models following the main
issues guided by the test questions. Student learning
gain was quantified as a percent of students in the trial,
who changed their answers from incorrect at pretest to
correct answer at posttest for each item.
The open-ended written questionnaire included five
questions and was given to 28 volunteer student groups
after they completed the multiple-choice questionnaire.
This evaluation process required some integration of the
details of the factual knowledge on DNA and protein
structures, which included in the multiple-choice questionnaire (1) Would Watson–Crick base pairs of different
orders, for example, A:T versus T:A, G:C versus C:G
affect the regularity of the sugar-phosphate backbone?
Explain your answer, (2) Draw the two complementary
DNA chains showing in detail the two deoxyribose-phosphate backbones, (3) How can you describe the nature
of the handedness of the B-form double helix, and its
grooves?, and (4) Draw a schematic diagram showing a
repeat of a helix with the number (n) of residues ¼ 4 and
2. In evaluating the open-ended questions, we looked for
the accuracy of their descriptive responses and the
number of student groups that could not answer the
questions descriptively at all.
In group interviews conducted by the first author after
the content questions, students were asked to answer
two additional questions, which directed them to talk
about the contribution of the physical models to their
learning (‘‘Do you feel more confident completing the
questions on DNA and polypeptides while handling this
set of models?’’ And ‘‘How different types of representation (e.g., textbook pictures, computer illustrations, other
physical models, and this set of models), used as
enabling tools, help facilitate your learning of the molecular structures?’’).
RESULTS AND DISCUSSION
The aim of this work was two-fold: (1) obtain quantitative
data in an effort to link student test performance with the
use of the physical macromolecular models in terms of
structures and (2) obtain qualitative data to corroborate the
quantitative data and to define the areas where students
have difficulty in understanding the material.
Factual Knowledge
Students’ factual knowledge was evaluated by means
of multiple choice questionnaire, which has nine questions on both DNA and the polypeptides. Questions and
responses to the pretest and posttest can be found in
Table I. The findings from the pre- and posttest survey
showed that in the pretest, only questions 1 and 5 were
answered correctly by more than 50% of the students,
whereas, in the posttest, the vast majority of them had
the correct answers for all nine questions.
The percentage difference in correct answers of postversus pretest for each question was also large: 26.7,
64.1, 42.2, 64.9, 42.2, 59.2, 68.7, 90.8, and 49.0 percent
for questions 1–9, respectively.
Analysis of students’ answers to the open-ended
questionnaire showed that similar to the findings from
the multiple-choice questionnaire, student performance
was significantly better on the pretest containing the
361
TABLE I
Questions and responses to the pretest and posttest multiple-choice questionnaire
Pretest
Questions
n
1. Which nitrogenous base pair is present in the same proportion in double-stranded DNA molecules?
1. Cytosine; Thymine
18
365
2. Thymine; Adeninea
3. Adenine; Guanine
27
4. Guanine; Cytosine; Adenine; Thymine
88
Posttest
%
n
3.6
73.3
5.4
17.7
0
498
0
0
%
0
100
0
0
2. Consider the Watson–Crick base pair below; there are the hydrogen bond donors and hydrogen bond acceptors. When accessing
the bases from the major groove what does one encounter—going from left to right?
1.
2.
3.
4.
Acceptor-donor-acceptor
Acceptor-acceptor-donor
Donor-acceptor-acceptora
Donor-acceptor-donor
269
32
136
61
54.0
6.4
27.3
12.3
9
2
455
32
18.1
0.4
91.4
6.4
3. Knowing that a glycosidic bond links the sugar to a base what is true for a Watson–Crick base pair in a duplex B-DNA molecule?
206
41.4
416
83.5
1. The beta-glycosidic bonds point in the opposite directionsa
2. The alpha-glycosidic bonds point in the opposite directions
222
44.6
82
16.5
3. The beta-glycosidic bonds point in the same directions
38
7.6
0
0
4. The alpha-glycosidic bonds point in the same directions
32
6.4
0
0
4. What will result from a 1808 flip of the principal axis of B-DNA structure?
1. Left-handed B-DNA
2. Right-handed B-DNAa
3. Left-handed Z-DNA
4. Right-handed A-DNA
268
155
57
18
53.8
31.1
11.5
3.6
2
478
3
15
5. Where is the principal helix axis of the ideal B-DNA located?
1. Through major groove
2. Through minor groove
3. Through the middle of the Watson–Crick base pairsa
4. Through P atoms in the backbones
121
77
288
12
24.3
15.5
57.8
2.4
0
0
498
0
6. The peptide bond in a perfect protein a-helix:
1. is planar.
2. is trans in configuration.
3. is rotatable about the single bonds linked to the a-carbon
4. Options 1, 2, and 3 are all correcta
85
308
62
43
17.1
61.9
12.5
8.6
132
21
7
338
26.5
4.2
1.4
67.9
7. In a typical a-helix of only 12 residues:
1. there are eight H-bonds.
2. the first four amide hydrogens do not participate in the helix H-bond.
3. the last four carbonyl oxygens do not participate in the helix H-bond.
4. Options 1, 2, and 3 are all correcta
213
87
166
32
42.8
17.5
33.3
6.4
9
17
98
374
1.8
3.4
19.7
75.1
8. The protein b-pleated sheet structure:
1. is pleated because the peptide bond is not planar
2. has the side chains of adjacent amino acids only on one side of the plane of the sheet
3. has the backbone which can be regarded as a helix with two residues per turna
4. makes a zigzag pattern perpendicular the chain directions
52
243
38
165
10.4
48.8
7.6
33.1
6
0
490
2
1.2
0
98.4
0.4
234
127
78
59
47.0
25.5
15.7
11.9
478
6
10
4
96.0
1.2
2.0
0.8
9. Which statement is true about the b-sheet backbone connection?
1. The shorter b-turn allows the sheet to reverse the direction of its polypeptide chaina
2. The longer crossover connection connects the antiparallel strands of the sheet
3. The H-bonds formed in the crossover connection structure are bent significantly
4. One or more b-strands may lie between the two strands connected by the crossover
connection but the latter never links the two nearest neighboring strands
n, no. of responses.
a
Correct answer.
0.4
96.0
0.6
3.0
0
0
100
0
362
BAMBED, Vol. 38, No. 6, pp. 359–364, 2010
TABLE II
Responses to the pretest and posttest open-ended content questionnaire
Pretest
(n ¼ 28)
Questions
1. Would Watson–Crick base pairs of different orders, for example,
A:T versus T:A, G:C versus C:G affect the regularity of the sugar-phosphate backbone? Explain your answer.
2. Draw the two complementary DNA chains showing in detail the two
deoxyribose-phosphate backbones.
3. How can you describe the nature of the handedness of the B-form
double helix, and its grooves?
4. Draw a schematic diagram showing a repeat of a helix with the
number (n) of residues ¼ 4 and 2
Posttest
(n ¼ 28)
C U ND NA
C U ND NA
3
2
22 5 0
1
8 15
4 21
1
2
21 6 0
1
2 17
6
3
23 3 1
1
2 23
0
3
25 2 0
1
n, no. of student groups; C, correct; U, unclear; ND, no description, NA, no answer.
same questions. The wider variability between students’
responses to open-ended questions was due to the level
of accuracy of their descriptive responses. There were
fewer student groups that did not answer some or all of
the questions. The findings from the pretest open-ended
questions shown in Table II indicated that some students
were not even aware of the following:
1. A nucleotide in a double helix is related to the
nucleotide lying across the helical axis from it in
the same plane by a pseudo two-fold axis of rotation and that the two types of Watson–Crick base
pair have exactly the same geometry.
2. When looked at end on, the relative rotation angle
between one base pair and the pair away from the
onlooker is 368 clockwise although students can
verbalize that one turn of the helix encompasses
10 base-pairs.
3. Each phosphate group makes two ester linkages:
one with the oxygen of C30 of the deoxyribose, and
one with the oxygen of C50 .
4. C10 of the sugar is covalently linked to the nitrogen
9 of a purine or the nitrogen 1 of a pyrimidine.
5. In the major groove, a large portion of nitrogenous
bases are exposed or more accessible.
6. Definition of a helix, especially a helix with two residues per turn.
Conceptual Learning
Results from the two assessment methods showed
that from their exposure to our models, even for a relatively short time, students gained relevant conceptual
knowledge of biomolecular structures. This is illustrated
by the following examples of student quotations.
‘‘Only Watson–Crick A:T, T:A, G:C, and C:G pairs allow
the construction of a regular double helix. This is
because of a size complementarity, the large bases
always pair with the small bases. We also noticed when
handling the base pair unit pieces of the DNA modeling
kit that the two types of base pair also have exactly the
same geometry, that is, AþT and CþG span virtually an
equal distance and space between the sugar-phosphate
backbones. Thus, assorted Watson–Crick pairings of the
bases do not perturb the arrangement of the sugars’’
(Response to item 1).
‘‘I understand better now the directionality of the DNA
chains after working with the physical model. The backbone has directionality because the phosphate group is
linked via oxygen to the 30 carbon atom of one sugar and
to the 50 carbon atom of the other’’ (Response to item 2).
Naturally, the two ends of a perfect DNA/RNA double
helix are identical in that both have the 50 and 30 ends
and there is at least a pseudo two-fold axis of symmetry
relationship between them: when looked at end-on both
helices are right-handed. For the a-helix, although it is
right-handed going from the N to C or C to N terminals,
the N and C terminals are different, and in going from C
to N and N to C one encounters things in opposite
orders. The same applies to the two different ends of
each strand of the nucleic acid double helix.
Another difficulty students have is in telling the 50 to 30
direction for DNA and the N to C direction for protein
from inside the chain, that is, not from the ends. For
DNA and RNA, they have to learn that C10 is bonded to
the base and C50 is outside the ‘‘plane’’ of the ring, thus
C30 can be identified more easily. The instructor may
make it more memorable (with no extra basic structural
learning) by saying that as a mnemonic: one goes up or
down the staircase of the major groove’s base pairs with
one’s right hand holding onto the 50 to 30 balustrade. For
polypeptides, it goes as N
Ca
CO and this is easy
to learn.
‘‘The model of protein a-helix with the guiding arrow
helps indicate the handedness and the direction of the
polypeptide backbone more clearly. When the instructor
asked me to look at each one end-on I found that when
the turn is clockwise then the helix is right-handed and
when it is anticlockwise, the helix sense is left-handed’’
(Response to item 3).
‘‘It is much easier than looking at the 2D illustrations
and seeing the chains turn to the right as they move
sideways, upward or downward’’ (Response to item 3).
The students were asked to look at each model endon and describe the helical turn further and further away
from the eye of the onlooker. When the turn is clockwise
then the helix is right-handed and when it is anticlockwise, the helix sense is left-handed. We have found this
to be much more efficacious in the long run than using
the left-handed or right-handed rule borrowed from
physics classes. One caveat, nowadays, with digital
363
watches and clocks, some students do not know which
is clockwise or anticlockwise.
‘‘The stacking of base pairs upon each other creates a
helix with two grooves because the single bonds formed
C10 of the two deoxyriboses, with the base pairs, on the
‘‘same’’ plane, make an angle lower than 1808, the
grooves are thus unequal in size’’ (Response to item 3).
‘‘I have learned about the major and minor groove
before, but I did not realize until now that each base has
a pattern of hydrogen bond acceptors and donors,
which, when the bases are stacked on top of one
another can offer a sequence that interacts with the
complementing amino acid side chains of an interacting
protein’’ (Response to item 3).
The differences between the major and the minor
grooves of the B-form double-stranded DNA cannot be
appreciated unless one scrutinizes a good model. In our
experience, a hand-held skeletal model is superior to a
computer-rendered one, even when the latter is rotatable
on the screen. Apart from the obvious differences in groove
size between the two polynucleotide backbones across the
major and the minor grooves, reaching the outer edges of
the base pairs from the major groove side is easier than
doing it from the minor groove side, which has different
parts of the bases partially blocked by the sugars.
The case for 3.6 residues per turn a-helical polypeptide deriving from 18 residues per 5 turns can be easily
made, whereas 3.6 residues per turn is not very convincing to students looking at a helix with only a few turns.
Six-tenths of a turn is difficult to arrive at. Also the helical
arrangement of the amino acid side chains can be easily
seen. Even in the case when the helix is not perfect one
can see how the amino acid side chains of a helical polypeptide can interact (more or less helically) with side
chains of another polypeptide chain, and/or the polypeptide backbone. The side chains can also interact with the
base-pairs of DNA or RNA or even the sugar-phosphate
backbone.
‘‘I have learned from the b-pleated sheet model of
polypeptide that for n ¼ 2, the helix degenerates into a
nonchiral backbone’’ (Response to item 4).
That the b-pleated sheet can be considered as a helix
so stretched that most backbone atoms are more or less
in the same plane could be made clearer to the students
with the hand-held models.
Student Model Building
Before we came up with the computer-printout models
as reported earlier [7], we used to ask groups of graduate students (4–5 per group) to make their own DNA
(A and B forms) or RNA (A-form) double helix from transparency film sheets on which the base pairs and the
sugar-phosphate backbone were drawn by the students.
All groups succeeded in correctly working out the proportion of the distance between successive base pairs,
helical diameter and helical repeat, so forth. Nevertheless, they reported having problems with the proper
folding of two sets of double-slanted parallel lines drawn
on a sheet which, when folded properly would give the
right-handed double helix with a major and a minor
groove. If folded the other way, the helical sense would
be wrong and the Watson–Crick base-pairs would not
link with the corresponding C10 of sugars.
For high school students, we usually give them
Watson–Crick base pair print-outs on the transparent
plastic top of the sweet container. These flat tops, each
with a hole in the middle, are then arranged with flat surface perpendicular to and along a drinking straw (acting
as the central axis) with pins for regularly separating the
base pairs. The backbone was given as a sheet of transparency with two sets of double-slanted parallel lines
(with sugar-phosphate structures as the backbone drawn
on them). Students are asked to fold this sheet of transparency to give a right-handed double helix. Again, they
have to learn how to fold the sheet properly as well as to
rotate the base pairs one after the other at a correct
angle (actually determined by two lines marked on the
transparency tops) relative to each other. Otherwise,
the backbone and the base pairs would not match. Here
also students learn a great deal by construction.
Although graphical models are relatively easy to find
on the internet, few of them offer clear information and
explanation about their physicochemical characteristics
and other contextual information for the needs of the
inexperienced beginning students [8, 9]. Thus, concrete
3D models should still be made available to students at
least in the introductory class to initially anchor the basic
understanding. A transition to the use of virtual computer
models can be made later on for better interactivity and
more precise bonding and structure values.
CONCLUSIONS
Utility of Models
The attitudinal data obtained provided clear evidence
that a majority of students reacted positively to the models and believed that their understanding improved when
handling this set of models. Most students elaborated on
the difficulties of understanding the abstract image of
structural diagrams found in textbooks. Those who had
additional experience in using molecular visualization
software stated that most freeware downloads, especially, the space-filling ones, did not provide much assistance to the inexperienced users, as found by others [8,
9]. Some students found that certain popular physical
models they had used could not give them an insight
into the atomic details.
Our models offer very tangible structural details that
students could learn by themselves or only with a little
guidance from the instructor. Features of the DNA double
helix, such as helical sense, base stacking, adjacent
base pairs’ relative rotation, major and minor grooves,
accessibility to hydrogen bond donors and acceptors,
backbone direction (50 to 30 ), and so forth, can be
grasped more easily.
We wish to elaborate more on accessibility to the
major and minor grooves. Apart from the obvious differences in the two widths of the B-form, the charged
phosphate groups, and the hydrogen bond donor and
acceptor parts of the various bases are the extras the
students can see easily and be used for their learning of
364
DNA interactions with groove-oriented drugs and protein
chains. It is worth pointing out that these grooves can
have one pseudo two-fold axis of symmetry, which can
selectively interact with molecules having a similar
symmetry. Naturally, intercalation by drugs and dyes can
be easily visualized because of the gap between base
pairs. However, distortion of the helical axis and base
pairs because of intercalation is not as dramatic as in the
space-filling models.
Our transparency-based computer printout models are
superior in many ways, for example, easily constructed
while having atomic details that can be looked at through
many base pairs or residues from both ends, and they
are also portable and robust. One possible drawback is
that the base pair thickness is not shown as can be seen
in some space-filling models, textbook, and computerbased illustrations. But the instructor can inform the students of the drawback and make corrective statements.
For a-helix and b-pleated sheet models, students can
also follow easily the backbone direction, adjacent amino
acids side chain relative positions, helical sense, etc.
The instructor may be reminded that in many proteins,
the helical and sheet parts may not be so perfect and the
axes can fold and wrap around other biomolecules.
As a result of using our models not only could students
answer the multiple choice questions better at posttest
but also describe verbally what they know more cor-
BAMBED, Vol. 38, No. 6, pp. 359–364, 2010
rectly, and at length, and with relatively fewer groups
unable to answer any question at all.
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