FAYETTEVILLE, Ark. - Researchers have refined the structure of the amino acid tryptophan, which will increase the accuracy of protein molecular modeling—essentialin creating new drugsand structure determination for medically important molecules.

The findings were reported in a recent issue of the Journal of the American Chemical Society by a team of researchers including three U of A faculty and three former students now involved in postdoctoral or graduate work at other institutions. They are University Professor of chemistry and biochemistry Roger Koeppe; Distinguished Professor of chemistry and biochemistry Peter Pulay; research professor of chemistry and biochemistry Denise Greathouse; Haiyan Sun, a postdoctoral associate at Johns Hopkins University, Patrick van der Wel, now a postdoctoral associate at Massachusetts Institute of Technology, and Erin Scherer, now a graduate student at Scripps Institute of Oceanography.

Work in protein structures, done by experimental modeling, x-ray crystallography or nuclear magnetic resonance spectroscopy (NMR), uses protein structure libraries to explore and explain the structure of biological molecules. Structure determines a molecule’s function, so researchers want to know structures as accurately as possible, particularly in proteins, which comprise a large part of medically important molecules. An accuracte description of a drug’s structure allows scientists to predict how it will interact with other substances in the human body.

The researchers used NMR to study how tryptophan influences certain types of membranes. To study tryptophan, they replaced the hydrogen atom with deuterium, a common marker used in such experiments.

The experimental results did not fit the commonly held "picture" of tryptophan with a hydrogen atom on the same axis as the carbon atom.

"The symmetric geometry would not fit the data," Koeppe said.

Instead, the experiment and three others like it indicated that the carbon-hydrogen bond makes a six-degree angle with respect to the symmetric plane. The researchers used theoretical energy calculations to test their findings and discovered that they support the experimental results indicating the six-degree angle.

"There’s a beautiful agreement between experiment and theory," Koeppe said.

Six degrees sounds small, but scientists assume that these angles are known to an accuracy of one tenth of a degree, so this difference represents a "chasm in bond angles," Koeppe said.

"We think most of these standard geometries were worked out long ago," Koeppe said. "But few researchers have really paid attention to the locations of the hydrogen atoms."

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