The scientists are using a version of this old trick to "watch" proteins fold. The "strobe light" is a temperature jump and the "camera" is a fast chemical reaction whose outcome is measured by a sensitive mass spectrometer.
Why folding is a complex problem
One of the dogmas of modern biology is that the sequence of amino acids determines how a protein will fold. If the amino acid sequence is known, it should be possible to calculate the protein's final structure from scratch.
But like many things in life, it's harder than it looks.
"Think of a protein as thousands of atoms connected together by springs," says Gross, who is also director of the National Institutes of Health/ National Center for Research Resources (NIH/NCRR) Mass Spectrometry Resource "If you were to suspend this object with a string from the ceiling and let it flop around, imagine how many shapes it could take."
"An enormous number, because it is free to move in so many different ways."
In practice, scientists often predict protein structure not from scratch but by analogy. They sift through large databases for proteins with similar sequences of amino acids and assume similar amino-acid chains will fold in similar ways.
"But," says Gross, "at some point any method for predicting protein structure has to be checked against experimental evidence that shows how proteins actually do fold."
That's what his research is all about.
A model protein for the experiment
Barstar is a small protein synthesized by a soil bacterium that is often used in folding studies.
Importantly, barstar's "native state" is known, as is its primary structure, the sequence of the protein subunits called amino acids of which it is made. What isn't known is how the amino-acid chain twists and coils
|Contact: Diana Lutz|
Washington University in St. Louis