"Excited!" was the first response from Ayyalusamy Ramamoorthy, when the 800 megaHertz nuclear magnetic resonance (NMR) spectrometer, built by Bruker Biospin Inc., was installed at the Department of Chemistry in summer 2017. A professor of chemistry and biophysics, Ramamoorthy explained that it is highly valuable for his work.
NMR spectroscopy is used to study the structure of organic molecules, from small molecules like potential new drugs to biomolecules such as proteins or nucleic acids. The information that can be extracted with an 800 MHz spectrometer allows researchers to study the structure and dynamics of complex biomolecules.
"NMR is one of the few techniques that gives you both structure and dynamics at the atomic level," said Sarah Keane, assistant professor of chemistry and biophysics. "It tells you how atoms are connected together, how they are arranged in space, and how they move relative to each other." Her lab uses diverse biochemical and biophysical techniques with a focus on NMR spectroscopy to study the atomic resolution of the structure of RNA and folding it undergoes.
At the heart of the NMR spectrometer is a powerful super-conducting magnet cooled close to 0° Kelvin with a jacket of liquid helium, in turn cooled by an outer jacket of liquid nitrogen. The magnetic field is powerful enough to levitate a frog.
This spectrometer will enable researchers to conduct experiments not possible with NMR machines with lower magnetic fields. It will also produce faster results, and studies can be conducted with much lower concentration samples. "If you are dealing with precious materials or natural products, you may have less than a milligram to work with," Ramamoorthy explained.
His lab uses NMR spectroscopy to study a challenging membrane protein called CytochromeP450. This enzyme is known for its ability to oxidize a wide range of compounds including more than 70% of marketed drugs. Given the complex and dynamic nature of this enzyme, NMR spectroscopy is the best tool to understand the how the structure of this enzyme changes over time. In addition, his lab uses NMR spectroscopy to study protein misfolding, a process in which proteins do not attain their desired 3D conformations, as well as toxic proteins implicated in Alzheimer's disease. The research team also investigates structure and function of biological solids such as amyloid fibers and bone.
The new spectrometer was purchased with a $2.7 million grant from the University of Michigan calling for collaboration among the colleges of LSA and Pharmacy, the Medical School, and Life Sciences Institute. Substantial preparations had been underway long before the new machine arrived on two tractor-trailers, along with ancillary equipment and installation gear. The floor of the room had to be reinforced with concrete using non-magnetic fiberglass rebar and the ceiling had to be raised to accommodate the instrument, but one cost-saving was that it did not require an entire new building. The Department of Chemistry core NMR Facility currently operates six other NMR spectrometers, which are regularly used by researchers across other departments on and off campus.