Using Computers to Unlock the Secrets of Molecules The West ...

USP BULLETIN: WEST CENTER PAGE 7
CHEMISTRY LAB. For many, the words
conjure up a bevy of images and memories:
the hiss of a Bunsen burner, scratched safety
goggles, and a lab filled with white coats
and unique aromas—where knowing how to
properly dispose of toxic waste is as important
as knowing the Periodic Table. It is this
atmosphere that drove a young chemistry
undergraduate into the University’s hub of
theory, the West Center for Computational
Chemistry and Drug Design. “It was the
thought of having to wear safety glasses that
drove me to Preston Moore’s office,” says
RAEANNE NAPOLEON C’05. “And,” she
adds upon consideration, “a love for theoretical
research and tackling big problems.”
A snapshot from the ab initio molecular dynamics
simulation of Zr4(OH)8(H2O)16, a Zr(IV) tetranuclear
species, important for the functioning of all
commercially available antiperspirants.
Using Computers
to Unlock the Secrets
of Molecules
The West Center for
Computational Chemistry
and Drug Design
BY SHAWN J. FARRELL
From left to right: Vojislava Pophristic, PhD; Preston
Moore, PhD; Randy Zauhar, PhD; Michael Bruist, PhD;
and (seated) Edward Birnbaum, PhD, chair of the
Department of Chemistry & Biochemistry.

An illustration representing the binding mode between
heparin, a widely used anticoagulant drug (yellow),
and a short aryl amide foldamer, a promising heparinantidote
(red), designed with the aid of molecular
dynamics simulations. Reprinted with permission
from Angewandte Chemie International Edition,
Volume 44, Issue 41, October 21, 2005.
It is this fascination with large theoretical
problems, problems that require the equivalent
of 128 computers to process, that Napoleon
shares with her research mentor and West
Center Director, PRESTON MOORE, PhD.
Dr. Moore is one of six full-time researchers
who use the West Center resources to apply
theoretical and computational methods to
chemical and biological problems. These
methods help researchers solve mathematical
models describing the nuclei and electrons
that make up small molecules like aspirin
and large protein molecules like hemoglobin.
As the mathematical models and computational
power improve, chemists will be able
to expand their ability to predict the behavior
of molecules. This, in turn, will allow
West Center researchers to solve many practical
problems, including simplifying the
design of new drugs.
VOJISLAVA POPHRISTIC, PhD, for
example, uses “molecular dynamics” computational
methods to advance her efforts
to develop an antidote to heparin, which
is widely used as an anticoagulant drug
for treatment and prevention of thrombosis.
RANDY ZAUHAR, PhD, on the other
hand, is developing a “shape signature”
computational method to tackle the problem
of designing drug molecules, or inhibitors,
against highly mutable targets such as
HIV protease.
Computational chemistry is a rapidly
growing field that is continually developing
more powerful computational tools to improve
the ability of these methods.
According to EDWARD BIRNBAUM, PhD,
chair of the Department of Chemistry &
Biochemistry, “As long as Gordon E. Moore’s
law is still applicable and we continue to
double computational speed every year or
so, we’re going to keep finding better ways
to do computational work.”
Recognizing the field’s potential and seeing
an opportunity to lead, the University
has made significant investments in staffing
and instrumentation over the last five years.
The result is a rare combination of caliber
and breadth, especially for such a small
department. “A typical department of chemistry
with 20 faculty members will have one
computational chemist,” says Dr. Moore.
“We have six.”
The West Center is also a rare forum for
researchers from disparate fields to come
together to work on common problems but
from different perspectives. “For example,
I’m doing molecular dynamic simulation,
which is one part of computational chemistry.
GUILLERMO MOYNA, PhD, is
doing electronic structuring, which is what
“Not only is the West Center
a vital resource for our own
researchers throughout the
University, but now with the
future possibility of short
courses, it also has great
potential for affecting our
industry partners nationally.”
SUSAN BARRETT
Assistant Vice President for
Corporate, Foundation, and
Alumni Relations
most people associate with theoretical
chemistry. MICHAEL BRUIST, PhD, is
investigating the dynamics of DNA in
DNA-protein structures and unusual DNA
structures, and ZHIJUN LI, PhD, is doing
bioinformatics homology modeling, which
is a way of determining protein structure
so that drugs can be designed virtually on a
computer,” says Dr. Moore. “It’s very diverse,
but all have a need for large computations.”
The National Science Foundation (NSF)
West Center Director, Dr. Preston Moore and Niny Rao, PhD.
cited USP’s concentration of expertise and
common need and its focus on collaborative
research as the major factors in its decision
to award the University a nationally competitive
Major Research Instrumentation
grant in 2004. “It was a feather in our cap,”
says Dr. Moore, “because USP’s proposal
was pitted against larger topflight research
institutions like University of Illinois and
Carnegie Mellon University.”
Awarded on merit alone, Dr. Moore’s
NSF grant allowed the University to purchase
a Beowulf Supercomputer Cluster
with the processing capability of 128 computers.
The NSF grant, although critical
to the advancement of the West Center,
built on the early accomplishments of Dr.
Birnbaum, who advocated for the establishment
of a center for computational chemistry
and secured the first successful grant
from the H.O. West Foundation.
Without the visionary generosity of
the H.O. West Foundation, Drs. Zauhar
and Moyna—USP’s first computational
chemists—would not have been able to
fashion the University’s first computer cluster
(20 CPUs) that established the center
that bears the foundation’s name.
On the momentum of this early and
steady success, the West Center is driving
forward. “Our immediate goals at the
West Center are threefold,” says Dr.
Birnbaum, “to reach out to the corporate
community with consulting services and
possibly a series of short courses in computational
chemistry, to expand the profile
and use of the center throughout the various
departments in the University, and to offer
more research opportunities to students,
particularly undergraduates.”
This latter effort is what allowed
Napoleon to contribute to research that has
culminated in three published papers and
one pending publication. Now a graduate
student at the University of Pennsylvania,
Napoleon says she feels lucky about “getting
in on the ground floor…when the West
Center was basically me and Dr. Moore.”
Napoleon cites
her research experience
at the West
Center as one reason
she feels she
has a jump on her
graduate school
peers. After three
years working with
Dr. Moore in the
West Center,
Napoleon has a
clearer sense of her
research interests.
As her own academic
career and
research interests
flourish,
so, too, does
the West
Center.
According to
Napoleon,
“Based on the
growth I’ve seen
over the past few
years, I have no
doubt that the West
Center is on the verge
of national recognition.”
Establishing the West
Center as a nationally recognized
center of excellence
is on the minds of everyone
involved with the center. SUSAN
BARRETT, MEd, assistant vice president
for corporate, foundation, and alumni
relations, works closely with the West Center
and shares its goals. “There are incredible
opportunities for everyone,” says Barrett.
“Not only is the West Center a vital resource
for our own researchers throughout the
University,” she notes, “but now with the
future possibility of short courses, it also
has great potential for affecting our industry
partners nationally.”
The West Center is now exploring how
best to offer a series of short courses in
computational chemistry and related areas
specifically geared for a corporate or industry
audience. These proposed one- to two-day
workshops will be designed to introduce
industrial scientists and managers to the
power of the methodology and the tools
used in computational chemistry and
improve the skills of scientists who are
already well versed in this methodology.
There’s no doubt that the West Center
is an active laboratory—having generated
over 20 published papers in the last two
years alone—but for now, it only has the
resources to process one large mathematical
problem at a time. As interest among
University and industry researchers grows,
time with the computer becomes a tighter
commodity. It’s a lot like astronomers
scheduling time at a mountaintop telescope.
With such a diverse group
A computer-generated
model of how a protein
inserts into a membrane.
The lipid-bilayer surface
area initially increases as
the protein makes contact,
followed by contraction as
the protein inserts into the
bilayer. Reprinted with permission
from Biophysical
Journal, May 2005,Volume
88, Number 5.
of researchers and students
vying for processing time,
it’s up to Dr. Moore to
arrange the schedule. When
asked how he manages this
task, Dr. Moore smiled
and replied, “We created an
algorithm.” Naturally.