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Jan 16, 2014

Music of the Proteins

Music of the Proteins

Scientists used a new imaging technique to observe the vibrations of lysozyme. This graphic depicts how lysozyme vibrates when it is excited by terahertz light (depicted by the wavy red arrow). [Andrea Markelz and Katherine Niessen]

  • Philosophers once spoke of the Music of the Spheres, the idea that the movements of celestial bodies express an underlying logic, and that astronomical measurements and mathematical relationships correspond to so many “tones.” Today, another sort of harmony, just as inaudible but perhaps just as beautiful, may characterize proteins. Proteins, it turns out, vibrate in different patterns. And these vibrational patterns may help proteins alter their structures, affecting everything proteins do, from the take up and delivery of oxygen to the “tuning” of membrane ion channels to the replication of DNA. Life itself, at the molecular level, may be a kind of symphony.

    Such music, consisting of molecular motions, may enable proteins to change their shape quickly so they can readily bind to each other. This idea has inspired investigations since the 1960s. They proved frustrating, however. To look at large-scale correlated motions in proteins, scientists had to impose extremely dry and cold conditions. Even worse, such studies required expensive facilities, noted Andrea Markelz, Ph.D., a physics professor at the University of Buffalo (UB). Some scientists, added Dr. Markelz, even adopted the view that a protein is more like a wet sponge than a bell: “If you tap on a wet sponge, you don’t get any sustained sound.”

    Fortunately, Dr. Markelz was not discouraged. Along with colleagues from UB and Hauptman-Woodward Medical Research Institute (HWI), Dr. Markelz used a new imaging technique to observe in detail the vibrations of a lysozyme, an antibacterial protein. The technique, which is based on orientation-sensitive terahertz near-field microscopy, exploits an interesting characteristic of proteins—they vibrate at the same frequency as the light they absorb.

    “Our technique is easier and much faster” than the techniques that had encumbered earlier investigations, said Dr. Markelz. “You don’t need to cool the proteins to below freezing or use a synchrotron light source or a nuclear reactor—all things people have used previously to try to examine these vibrations.”

    The findings appeared January 16 in Nature Communications, in an article entitled “Optical measurements of long-range protein vibrations.” In this article, the authors wrote, “Underdamped modes are found to exist for frequencies >10-1. The existence of these persisting motions indicates that damping and intermode coupling are weaker than previously assumed.” This finding, the article emphasizes, represents the “first optical observation of long-range protein vibration modes.”

    To study vibrations in lysozyme, the team exposed samples of chicken egg white lysozyme single crystals to light of different frequencies and polarizations, and measured the types of light the protein absorbed. This technique, developed with Edward Snell, a senior research scientist at HWI and assistant professor of structural biology at UB, allowed the team to identify which sections of the protein vibrated under normal biological conditions. The researchers were also able to see that the vibrations endured over time.

    In their article, the researchers concluded that their technique “permits protein engineering based on dynamical network optimization.” For example, the technique could be used to document how natural and artificial inhibitors stop proteins from performing vital functions by blocking desired vibrations. “We can now try to understand the actual structural mechanisms behind these biological processes and how they are controlled,” explained Dr. Markelz.

    “The cellular system is just amazing,” Dr. Markelz declared. “You can think of a cell as a little machine that does lots of different things—it senses, it makes more of itself, it reads and replicates DNA, and for all of these things to occur, proteins have to vibrate and interact with one another.”

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