Download Using Computers to teach Undergraduates about Biological Molecules

Biochemical Society Transactions ( 1 996) 24
Using Computers To Teach Undergraduates
About Biological Molecules
Christopher A Smith, Alan H. Fielding, M. Odette McCormick,
Jeremy Murray and 'Claire E Sanson. Department of Biological
Sciences, The Manchester Metropolitan University. Manchester,
M 1 5GD. UK and 'Department of Biochemistry and Molecular
Biology, University of Leeds, Leeds. LS2 9JU.UK.
Computers have a variety of educational uses. In teaching
Biochemistry to undergraduate students at The Manchester
Metropolitan University we have made relatively extensive use of
computers to emphasize the structures and functions of biological
molecules. This teaching is within the context of the Biological
Sciences and often to students whose main interests are in Biology
rather than Chemistry and the Physical Sciences. Further, we try to
ensure that computer-based teaching is integrated with traditional
approaches, such as lectures to impart basic material, tutorials to
reinforce learning and wet practicals to develop the motor,
observational. planning and communicative skills associated with
scientific rigour [I].
We have concentrated mainly on using bioinformatics and
molecular modelling computer packages. Bioinformatics can be
described briefly as the computer-based analyses of onedimensional information about biological molecules. This
information typically consists of the primary structures of nucleic
acids and proteins. Molecular modelling, as the term implies, is the
use of computers to model the structures, properties and functions
of biomolecules. In Biology, function is a consequence of structure
and, since primary structure determines the higher order structures
of proteins, it follows that bioinformatics and molecular modelling
are interlinked disciplines. Desk top computers are becoming ever
more powerful and, perhaps more importantly given the financial
constraints imposed upon higher education, cheaper. Thus,
although a number of our applications of computers in the delivery
of tutorials and practicals and in student-based project work are
now well established, others are constantly developing as newer
computers and programs become available.
We use bioinformatics mainly in simple sequencing
exercises and in the prediction of the secondary structures of larger
peptides and proteins. Sequencing and primary structure are
emphasized using the Protein Sequencing program from IRL
Software (IRL Press, Eynsham. UK). This program generates
random sequences of M, about 14OOO or can have specific
sequences added to it. Primary structures may be completely
determined by simulating traditional protein biochemical
approaches. Students can normally determine the sequence of a
polypeptide of 70-80 residues in about two hours. Reasonably
realistic yields and 'carry over' contaminations make this an
attractive program despite its age.
The utility of prediction methods in teaching protein
In addition, the
structure have been emphasized elsewhere [2-41.
whole organism genome programmes currently extant [5]means
that the subject is experiencing a renewal of interest. The subject
has been extensively reviewed [6].We routinely employ the
predictive algorithms of Chou & Fasman, 1978 and the O R
method [7.8]among others. The comparative wealth of structural
information reported for larger peptides and proteins in journals
such as Structure and Nature Structural Biology and summarized
in the excellent texts, Macromolecular Structures 1991 -1994 [9]
means that each student can be assigned a specific peptide/protein,
be required to predict its secondary structure by one or more
methods and then assess the accuracy of the prediction [ 10-121by
comparison with the known structure. When using this approach in
practical classes or as a tutorial exercise we have tended to use
only peptides of less than about 60 residues and require both
123s
'manual' Chou-Fasman and computer-based GOR predictions. The
commercially available version, Protean I1 (Proteus Molecular
Design, Marple, Stockport, UK) also assigns putative 9.w angles
and so the predicted secondary structure can be visualized using
molecular modelling packages (see below). Prediction lends itself
particularly well to bioinformatics projects, such as assessing the
relative merits of different predictive algorithms with a restricted
number of proteins of known structure; identifying the
uansmembrane regions of integral membrane proteins or assessing
the value of a specific algorithm using an extended number of
proteins of known structure.
Traditionally, molecular modelling has relied upon powerful
workstations or expensive minicomputers. However, a large
number of accessible programs, for example Alchemy, Moby,
HyperChem, are now available for a variety of microcomputers.
We use a very simple program, the SSERC Chemical Modeller
(SSERC, Edinburgh, Scotland, UK) to illustrate basic graphical
features such as building simple molecules, visualizing and
manipulating stick, ball & stick, dot surface and space-fill models.
Modelling at this level is particularly good at illustrating
fundamental conformational features such as D- and L-isomers,
a-and P-anomers or cislrrans double bonds in fatty acids.
HyperChem (Autodesk Inc, Sausalito, California, USA)
offers a half-way house between the simpler microcomputer-based
systems and the comprehensive, normally expensive, commercial
modelling packages such as those from Biosym, Chemical Design,
Molecular Simulations and Tripos etc. It is particularly useful since
it operates in a Windows-type environment with which many
students are familiar. In addition to using this program to teach
basic features of molecular graphics and computational chemistry,
it has proved its value in a number of final year student projects in,
for example, investigating the conformations of peptides by energy
optimization and molecular dynamics. The structures of many
peptides are known and these are often structurally interesting, for
example in possessing D-amino acids and modified termini,
despite their relatively small sizes.
Clearly computer-based teaching will become ever more
important in Biochemistry and related disciplines. We would be
grateful for any criticisms, comments or advice readers may care to
offer on the topic!
Please note, lack of space has precluded any graphics in this
article. However, we are happy to supply figures illustrating the
examples discussed to anyone who is interested.
REFERENCES
1 Smith, CA er al(l995)Biochem Educ, 23.69-71
2 Hider, RC and Hodges, SJ (1984)Biochem Educ, 12,9-18
3 Foguet, M and Aviles, FX (1989)Biochem Educ, 17.36-41
4 Smith, CA et al(l992)Binary, 4,156-161
5 Jones, SJM (1995)Curr Opin Genet Dev, 5,349-353
6 Fasman, GD (ed) (1989)Prediction of Protein Structure and
the Principles of Protein Conformation, Plenum Press, London
7 Chou, PY and Fasman, GD (1978)Ann Rev Biochem, 47,
251-276
8 Robson, B and Gamier, J (1986)Introduction to Proteins and
Protein Engineering, Elsevier, Amsterdam
9 Hendrickson, WA and Wuthrich, K (eds) (1991-1994)
Macromolecular Structures 1991 (and 1992-1994).Current
Biology Ltd, London
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1 1 Russel, RB and Barton, GJ (1993)J Mol Biol. 234,951-957
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