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Not only will this discovery sharpen our basic
knowledge of biology, Rodriguez said, but it also could help
scientists with a number of practical problems - such as selecting the
best potential new drug compounds from a vast group of candidates, a
process that can cost pharmaceutical companies years of work and
millions of dollars.
"Whereas we have had to be satisfied with observing
the chemistry in living things and describing it afterward without
complete understanding, we are developing computational tools that can
predict what will happen between molecules before they meet in the
test tube," said Rodriguez, who is an assistant professor of physics
in Purdue's College of Science. "Not only does this research open up a
new field of science that reveals how metalloproteins and their
constituent particles interact, but the quantum theory behind it also
should allow us to model and predict these behaviors accurately with
computer simulation alone. It is an example of how much can be
accomplished with interdisciplinary science."
Rodriguez is pioneering a new field he calls "quantum
biochemistry" - a field that involves both biochemistry and particle
physics, which are often cited among the more formidable subjects
science students tackle. Ordinarily, the two disciplines share little
common ground. Although biochemistry deals with interactions among the
complex molecules that our bodies use for the fundamental processes of
life, these microscopically small molecules are nonetheless gargantuan
entities in comparison with the tinier subatomic particles such as
protons and electrons that physicists study.
"Despite these differences, there is one point of
overlap between chemistry and physics that has interested me, and that
is in the elementary particles that whirl about these molecules - the
electrons," Rodriguez said. "Physicists have long known that,
according to the laws of quantum mechanics, there are some chemical
reactions in our bodies that are 'forbidden' - such as hemoglobin's
binding oxygen in our lungs when we breathe. But they do happen
nonetheless. So, because these reactions involve electron spin, we
decided to take a closer look at them."
Charge is a familiar property of an electron, but
it is not the only one. Electrons also have another quantum property
called spin, and though they are all negatively charged, they can spin
in one of two opposing directions - up or down.
"Nature loves balance, and you see evidence of it
in both charge and spin," Rodriguez said. "For example, electrons of
opposite spin like to pair up with each other as they fly around the
nucleus. This allows their spins to balance one another, just as
positive and negative charges do between protons and electrons. Even
when you have hundreds of electrons forming an immense cloud around a
complex molecule, you still see balance in both charge and spin; we
call this balance 'conservation,' and it's something we count on in
both chemistry and physics to help us understand these tiny objects.
"But sometimes the electrons in metalloproteins
seem to be playing a trick on us. As we see with hemoglobin, nature
appears to be conserving electronic charge while sacrificing this
conservation in spin."
Hemoglobin's active center contains iron, one of
the so-called transition metals. These metals are noted for the way
several of their electrons can fly around the nucleus unpaired.
When a red blood cell encounters oxygen in our
lungs, its hemoglobin is able to grasp some of the oxygen with some of
these unpaired electrons, carrying it to the rest of our body. But in
the process, the cumulative spin of the system changes in a way that
is not conserved, which to a physicist looks as strange as a ball
hitting the water without making a splash.
"This chemistry is vital for life, but physicists
wonder how it can happen," Rodriguez said. "The charge between the
electrons in the bonded oxygen and hemoglobin is balanced in the end,
which makes sense to chemists. But the electronic spin of the entire
system is not conserved, making a physicist frown at what appears to
be a formally forbidden process. Of course, we needed to learn more
about nature at the microscopic level."
As many of these supposedly forbidden reactions
involve biomolecules centered upon transition metals, which can flip
back and forth between different spin states under certain conditions,
Rodriguez theorized that it was this variability in spin state that
was influencing the rate of these reactions. To explore whether this
effect, which Rodriguez calls spin-dependent reactivity, was indeed
the decisive factor, the team is modeling the reaction rates with a
supercomputer, the only tool capable of keeping track of the motion of
so many particles at once.
"Supercomputers have allowed us to check our models
against our understanding of spin's effect on a reaction, and our
models have been closely checked by experiment," Rodriguez said. "The
results suggest that our understanding of electron behavior is
sufficient to create virtual models of molecules that we can then 'react'
with one another in simulations that accurately predict what will
happen when they meet in the physical world."
Rodriguez said the approach, though still in its
nascent stages, could provide insight into far more biologically
important molecules when it is further developed.
"We are at the point where we have developed
computational tools to analyze the spin-dependent processes of
biomolecules and have applied them to a few important test cases," he
said. "But our methods are based on approaches that are valid for any
molecular system. Therefore, hundreds more metalloproteins that are of
great scientific and practical interest may be studied in the future
with the methods we have developed."
For example, Rodriguez is planning to study the
manganese involved in photosynthesis to understand how water is broken
down to produce molecular oxygen. But for now, he is happy that the
four years of work his team has put into the project have produced
such encouraging results.
"We are creating a new field that attempts to
understand biochemical processes at the most fundamental level - that
of quantum mechanics," he said. "It could be the most important step
toward making biochemistry a predictive science rather than a
descriptive one."
Two papers on the subject, one of which Rodriguez
authored with Purdue's Teepanis Chachiyo, appear in this week's issue
of the Journal of Biological Chemistry. Jeffrey Long, a professor of
chemistry at the University of California at Berkeley, commented on
Rodriguez's work. "Rodriguez has come up with an elegant means of
evaluating excited-state electronic structures," he said. "It lends
insight to the detailed mechanisms of poorly understood
transformations in inorganic complexes." |
