Figuring out a protein’s role in life is difficult without its three-dimensional structure. And, more often than not, obtaining a structure involves coaxing a protein to form a crystal large enough and ordered enough to diffract x rays sharply.
X-ray crystallography is remarkably successful. So far, about 3000 x-ray-derived structures of human proteins have been deposited in the Worldwide Protein Data Bank. But our bodies make at least as many different kinds of protein as we have genes, about 35 000. Subjecting this sum, the human proteome, to structural analysis is clearly a task for automation.
Ambitious plans exist to crank through the proteome, but they could be frustrated by the reluctance of many proteins to crystallize. Some proteins, notably the transmembrane channels and transporters, defy crystallization because they don’t dissolve well in either polar or nonpolar solvents. But for other proteins, it’s hard to tell why crystallization is so...
