Researchers Use Neutrons to Solve Protein Structures

KNOXVILLE — The tiny particles known as neutrons — like the ones to be produced at the new Spallation Neutron Source — may be the key to understanding the structure of complex molecules, according to a new University of Tennessee study.

The most common atoms in biological molecules such as proteins, hydrogen atoms have been notoriously difficult to find as scientists have worked to understand the structure of the complex molecules.

This caused problems for scientists using traditional research methods for solving structures, according Chris Dealwis, UT associate professor of biochemistry. That’s why Dealwis, UT biochemistry professor Liz Howell and graduate student Brad Bennett explored whether using neutrons as a tool would help make the elusive hydrogen atoms easier to find.

Their work, published in a recent issue of the Proceedings of the National Academy of Sciences (PNAS), showed that neutrons can get the job done.

“Neutrons can see things that X-rays can’t,” said Dealwis.

Dealwis and Bennett’s research provides critical proof that the neutrons produced at Oak Ridge National Laboratory’s Spallation Neutron Source will be useful to other scientists who want to do similar work to understand how similar molecules are put together.

According to Dealwis, understanding the structures of these complex molecules helps scientists better understand how they are built and how they might interact with other molecules. One common use for the technique is to study drug molecules to understand how to make them more effective.

For their research, Bennett and Dealwis looked specifically at a drug molecule known as methotrexate, a drug most often used in chemotherapy.

The researchers used neutron scattering to understand the mechanisms of how the drug molecule attaches to a protein called dihydrofolate reductase (DHFR) from E. coli bacteria. Howell, an expert in DHFR, provided key insight for this work, according to Dealwis.

The neutron analysis for the research was conducted at the Los Alamos National Laboratory’s Neutron Scattering Center. Dealwis noted that the success of this work bodes well for the SNS, which produces a much more powerful stream of neutrons.

Their work was able to provide a greatly increased understanding of how the drug is put together, especially where the hard-to-find hydrogen atoms come into play.

“Now we know that spallation neutrons can be used to determine these protein structures,” said Dealwis, “The added flux that SNS can provide will increase the resolution and efficiency of the process.”

The SNS, which was first activated in April, 2006, is undergoing fine tuning as it is brought up to full speed over the coming months.

Dealwis, Howell and Bennett’s article can be found in the online edition of PNAS at


Chris Dealwis (865-974-4088,
Jay Mayfield (865-974-9409,