Structural biology is one of the most exciting areas of biochemistry,
but one that can be very difficult for students to grasp. The
basic premises of structural biology are not complex. Briefly,
structural biology is the study of the three-dimensional structures
of biological molecules. These structures are determined by identifying
the locations, in three dimensions, of all of the atoms (usually
several thousand of them) in a macromolecule. This is accomplished
by a process called x-ray crystallography. Recent advances in
crystallographic techniques enable crystallographers to determine
these structures at unprecedented rates. The value of determining
such structures lies not only in improving our understanding of
how an individual macromolecule works, but also in analyzing how
biomolecules interact with one another. This especially has had
an impact on drug design, as structural biologists can now design
drugs that will specifically interact with the macromolecule of
interest.
The difficulty in structural biology arises when students are
required to try to imagine these structures. All biochemistry
textbooks rely heavily on pictures to assist students with this
task, but students still have difficulty in translating a two-dimensional
picture into a three-dimensional structure. To address this, many
textbooks have supplemental multimedia applications that contain
three-dimensional structures that the students can manipulate
on their computers. I have found that many of these multimedia
supplements are very general and superficial, and do not sufficiently
direct the student's attention to the relevant parts of the molecules.
Therefore, it would be much more useful to have a computer program
that could be tailored to the class. The ideal system would be
based on the Internet, for immediate dissemination, and would
be free, since we all have very limited budgets.
I already use some technology in my introductory class on cell
biology and in a more advanced biochemistry course on macromolecular
structure. I currently show the students the structures I'm talking
about during class using Rasmol (http://www.umass.edu/microbio/rasmol/),
a molecular visualization program. This software can show, in
three dimensions, the structure of any available macromolecule.
These structures can be downloaded, for free, from Brookhaven
National Laboratory (http://www.pdb.bnl.gov/).
While the students really appreciate being able to see these structures
in three dimensions, using Rasmol is of limited utility, since
the students see these structures only during class. Ideally,
they would also be able to look at these structures outside of
class and while studying. While Rasmol is free and readily available,
it not ideal for independent student use, since it has a steep
learning curve. I want my students to spend their time learning
the structures, not the software. The solution to this problem
is Chemscape Chime.
Chemscape Chime, produced by MDL Information System, Inc. (http://www.mdli.com/),
is a Netscape plug-in that allows the "live" manipulation
of chemical structures within web pages. This program is free
to students and academics, as is the Netscape browser (http://home.netscape.com/).
It is based on Rasmol, so the scripting language is the same.
The advantage is that since it is Web-based, it is immediately
available to all students. It also has a simplified interface.
I can write a script to focus on a structure in Chime, and all
a student has to do is push a button to run it. Also, since it
is embedded in web pages, I can put a lot of explanatory text
into the page along with the structures, so that students can
see the structures and read about them at the same time. Using
Chime, Netscape, and the Brookhaven databases, all of the necessary
information and software to design a precisely tailored web-based
tutorial in macromolecular structure is available and free.
Two summers ago, I began to design a web-based tutorial using
Chime. This initial trial can be seen at
http://www.centre.edu/academic/programs/bmb/bmb31/tutorial/main.htm.
I have not used this tutorial in class yet, as it is too unfinished.
However, the students to whom I have shown it have all been very
enthusiastic. I am confident that they would find the complete
tutorial very valuable. I intend to integrate the tutorial into
my courses as either a homework assignment or as part of a laboratory
assignment. Ideally, I will include an on-line quiz over the structures,
that can be graded by the computer and automatically record not
only who has taken the tutorial but also how they have done.
I would like use the summer of 1998 to revise and complete this
tutorial to include not only protein structures, but also lipids,
carbohydrates, and nucleic acids and interactions between these
different types of macromolecules. I plan to design the tutorial
with different levels, so that students in an introductory biochemistry
course would use the sections of the tutorial that were relevant
to them, while more advanced students would investigate the entire
tutorial. In addition to designing my own topics, I also plan
to provide links to other Web sites that have Chime based tutorials.
The software needed to carry out this project is readily available,
as noted. Should I need any help with the programming aspects
of the tutorial, Centre's Computer Services department has several
people who are very good web designers. I plan to assess the tutorial
by including an assessment form in the tutorial itself, so that
anyone who uses it can provide immediate feedback to me. In addition,
I plan to use this tutorial during the 1997-98 academic year in
both an introductory cell biology class and a macromolecular structure
class. I will have students in both of these classes fill out
anonymous evaluation surveys.
This tutorial, since it is Internet accessible, would be available for immediate use by all members of the ACS. A quick review of the on-line catalogs for the ACS schools indicates that most of them offer one or more biochemistry or cell biology courses where this tutorial would be useful. In addition, once I have thoroughly learned this technology, I would be interested in offering a workshop in the summer of 1999 to teach other members of the consortium to design web sites tailored to their classes.