A new study is a "major step
forward" in the understanding of water-protein interactions. It answers a
question that's been dogging research into protein dynamics for
decades.
Credit: Jo McCulty
Scientists are getting closer to directly observing how and why water is essential to life as we know it.
A study in this week's Proceedings of the National Academy of Sciences provides the strongest evidence
yet that proteins--the large and complex molecules that fold into
particular shapes to enable biological reactions--can't fold themselves.
Rather, the work of folding is done by much smaller water molecules,
which surround proteins and push and pull at them to make them fold a
certain way in fractions of a second, like scores of tiny origami
artists folding a giant sheet of paper at blazingly fast speeds.
Dongping Zhong, leader of the research group at The Ohio State
University that made the discovery, called the study a "major step
forward" in the understanding of water-protein interactions and said it
answers a question that's been dogging research into protein dynamics
for decades.
"For a long time, scientists have been trying to figure out how water
interacts with proteins. This is a fundamental problem that relates to
protein structure, stability, dynamics and--finally--function," said
Zhong, who is the Robert Smith Professor of physics at Ohio State.
"We believe we now have strong direct evidence that on ultrafast time
scales (picoseconds, or trillionths of a second), water modulates
protein fluctuations," he concluded.
Zhong, who is also a professor of chemistry and biochemistry, and his
team used ultrafast laser pulses to take snapshots of water molecules
moving around a DNA polymerase, the kind of protein that helps DNA
reproduce.
The key to getting a good view of the interaction was to precisely
locate optical probes on the protein surface, he said. The researchers
inserted molecules of the amino acid tryptophan into the protein as a
probe, and measured how water moved around it.
Water molecules typically flow around each other at picosecond
speeds, while proteins fold at nanosecond speeds--1,000 times slower.
Previously, Zhong's group demonstrated that water molecules slow down
when they encounter a protein. Water molecules are still moving 100
times faster than a protein when they connect with it, however.
In the new study, the researchers were able to determine that the
water molecules directly touched the protein's "side chains," the
portions of the protein molecule that bind and unbind with each other to
enable folding and function. The researchers were also able to note the
timing of movement in the molecules.
Computer simulations at the Ohio Supercomputer Center (OSC) helped
the researchers visualize what was going on: where the water moved a
certain way, the protein folded nanoseconds later, as if the water
molecules were nudging the protein into shape.
Water can't arbitrarily shape a protein, Zhong explained. Proteins
can only fold and unfold in a few different ways depending on the amino
acids they're made of.
"Here, we've shown that the final shape of a protein depends on two
things: water and the amino acids themselves. We can now say that, on
ultrafast time scales, the protein surface fluctuations are controlled
by water fluctuations. Water molecules work together like a big network
to drive the movement of proteins."