Spotlights on Recent JACS Publications ■ PROTEIN FOLD BOUNCES BACK AFTER THE PRESSURE IS OFF

Martin Gruebele, Klaus Schulten, and colleagues show that a protein domain can refold rapidly after it is denatured by a sudden pressure increase (DOI: 10.1021/ja412639u). Understanding the kinetics of protein folding is fundamental to biochemistry. Researchers have used molecular dynamics simulations to capture the short time scale on which a protein refolds in response to brief temperature-induced denaturation. But comparatively few studies have used pressure perturbations to examine protein folding dynamics. In this work, the authors have determined, by experiment and a molecular dynamics simulation, how an 80-residue protein domain responds to a microsecond-scale burst of 5 kbar of pressure. They find that the protein domain almost completely refolds after about 19 μs, with the exception of one helix formation at the end of the polypeptide chain. The work provides new insights into how proteins refold after pressure-induced denaturation. It also sheds light on how proteins pass through transition states in the process of folding. Deirdre Lockwood, Ph.D.