Close-Up View Of Protein Folding

Two new studies—one computational, one experimental—examine the folding of individual proteins, finding that in many cases, repeated foldings tend to move along a prescribed pathway rather than taking many different possible routes. They also find that the folding processes are even more complex than previously thought, with intricate intermediate steps playing important roles (Science, DOI: 10.1126/science.1208351 and 10.1126/science.1207598). Kresten Lindorff-Larsen and colleagues at D. E. Shaw Research used the company’s supercomputer, Anton, to perform folding simulations of 12 proteins ranging from 10 to 80 residues long. The proteins begin to assume their biologically active shapes relatively early in the folding process, they found. Meanwhile, Matthias Rief and colleagues at Germany’s Technical University of Munich attached each end of a single calmodulin protein to tiny glass beads. The beads could then be manipulated with laser beams, allowing the group to probe the protein as it was stretched and unstretched. The identification of defined intermediates “highlights the power of single-molecule techniques,” Tobin R. Sosnick and James R. Hinshaw write in an accompanying perspective.