NEWS OF THE WEEK
BIOPHYSICS: Speedy protein stretching validates computer work
HE DETAILED WORKINGS of biomolecules as they generate and respond to mechanical forces can be analyzed effectively with computer simulations and experimental techniques. When examining things such as the way proteins unfold when muscles stretch, the two quite different approaches could complement one another. But the techniques up to now have worked on different timescales—experiments are slower—making it hard to combine their results. A technique called high-speed force spectroscopy now boosts experimental speed, allowing protein-unfolding information from simulations and experiments to be combined directly for the first time. The method was developed by Simon Scheuring of the French National Institute of Health & Medical Research (INSERM) at Aix-Marseille University and coworkers (Science 2013, DOI: 10.1126/science.1239764). The researchers demonstrated high-speed force spectroscopy on titin, a multidomain, springlike protein that unfolds to let muscles extend from a flexed position. “High-speed force spectroscopy will enhance experiment-simulation complementarity,” says computational biophysicist Klaus Schulten of the University of Illinois, Urbana-Champaign (UIUC). Development of the new technique “is an exciting milestone,” adds Julio M. Fernandez, a force spectroscopy pioneer at Columbia University. Molecular dynamics calculations on all the atoms in a protein such as titin are so computationally demand-
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ing that even today’s most powerful computers can simulate unfolding only for vanishingly brief moments. Such simulations generate movies of the molecular details of protein unfolding by pulling proteins apart at speeds Gold-coated support of a few millimeters per second. Experiments that use atomic force microscopy (AFM) or optical tweezers to measure energies and distances Titin when proteins are pulled apart physioctamer cally can operate only at speeds of about 100 nm/second at best—three to four orders of magnitude more slowly. The new technique boosts experimental speed to 4 mm/second, moving experimentation into the Cantilever same time regime as simulations. Key to the faster speed is a shortened AFM cantilever, a tiny probe that pulls proteins attached to it when it is deflected. The SLED shortened cantilever moves faster and pulls tethered proteins more quickly than conventional ones. Photodiode “There has been a lingering doubt about how much molecular dynamics simulations can really tell us because of the huge mismatch in timescale relative to experiments,” comments UIUC’s Taekjip Ha, an expert in single-molecule imaging and manipulation. Thanks to the new work, Ha says, agreement between simulation and experiment is now “impressive and deeply satisfying.” The technique can analyze how proteins respond to forces over a range of speeds, yielding what is called an “unfolding energy landscape.” It should also be useful for studying other force-related biological processes such as lipid-membrane dynamics and receptor-ligand unbinding, the researchers note.—STU BORMAN
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Cantilever
Light from a superluminescent light-emitting diode (SLED) is focused on a cantilever and detected by a photodiode to measure forces on a titin octamer as it is pulled between the cantilever and a stationary support.
PUBLISHING Cynthia J. Burrows named new editor of Accounts of Chemical Research The next editor-in-chief of the American Chemical Society journal Accounts of Chemical Research will be Cynthia J. Burrows, a chemistry professor and chair of the chemistry department at the University of Utah. ACS, which also publishes C&EN, made the announcement last week with an effective date of January 2014. Burrows will succeed Joan S. Valentine, a professor of chemistry and biochemistry at the University of California, Los Angeles. The journal publishes concise over-
views of basic research and applications in chemistry and biochemistry as well as special issues on single topics. The journal “has a rich history of providing scholarly essays on frontier areas of research,” Burrows notes. Accounts is a “unique venue for communicating the excitement of the chemical sciences, both in core areas of chemistry and at the interfaces with biology, medicine, materials, and energy research.” Burrows’s keen insight across many disciplines will serve her well, says Susan
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King, senior vice president of the ACS Journals Publishing Group. Valentine dedicated 19 years to serving as editorin-chief, “positioning the journal as a leading resource for the global multidisciplinary chemistry community,” King adds. Burrows earned a B.A. in chemistry from the University of Colorado, Boulder, in 1975 and a Ph.D. in chemistry from Cornell University in 1982. Her research covers organic and biological chemistry, with a focus on chemical modifications of DNA and RNA bases.—SOPHIE ROVNER
ADAPTED FROM SCIENCE
MATCHING PROTEIN EXPERIMENTS TO SIMULATIONS
