Small water molecules control protein motion, a new study published in the Proceedings of the National Academy of Sciences has found.
According to Zhong et al, water molecules control protein motion. Image credit: Rony Michaud.
The new study, led by Ohio State University researcher Dongping Zhong, 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.
“For a long time, scientists have been trying to figure out how water interacts with proteins,” Prof. Zhong said.
“This is a fundamental problem that relates to protein structure, stability, dynamics and – finally – function.”
“We believe we now have strong direct evidence that on ultrafast time scales (picoseconds, or trillionths of a second), water modulates protein fluctuations.”
The scientists 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,” Prof. Zhong said.
He and his colleagues 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, the scientists 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, they 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.
They were also able to note the timing of movement in the molecules.
Computer simulations helped the team 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. Proteins can only fold and unfold in a few different ways depending on the amino acids they’re made of,” Dr. Zhong said.
