A Daunting Challenge
McPherson has reason to be skeptical. Mass-producing protein structures is going to be a lot tougher than DNA sequencing. DNA is a simple linear code of four chemical letters, while proteins are composed of twenty different amino acids and fold into complex, largely unpredictable arrangements of sheets and loops. Although scientists have long tried, with the help of computers, to predict protein structure directly from the DNA blueprints, they’re still a long way off, even for the simplest proteins (See sidebar: “Blue Gene vs. Proteins”).
Instead, both Syrrx and SGX will be attempting to automate the most widely used empirical approach, known as X-ray crystallography. With this method, a protein is first purified, then coaxed to form a crystal. At that point, scientists shoot concentrated radiation into the crystal, exploiting the pattern of scattered rays to reconstruct an atom-by-atom model of the protein in its crystalline form.
Although that process may sound straightforward, it’s not. Many proteins, for instance, are extremely difficult to isolate, and the crystallization process itself is anything but cookbook. Temperature, acidity and salts must be fine-tuned to cajole a tiny, delicate crystal out of solution. Finally, converting the X-ray data into a three-dimensional model of a protein’s shape is often an “agonizingly difficult” problem, says University of California, San Diego crystallographer Lynn Ten Eyck. “There’s a lot of human judgment applied to that problem at present,” he says. “And human judgment takes time.”