New method uses computers in designing proteins

Researchers at the Medical Center recently introduced a new method of envisioning and producing proteins that could potentially be used for psychiatric treatment and ecological indicators.

Associate Professor of Biochemistry Homme Hellinga, whose study was published in Nature, incorporated a novel use of a computer program to specifically target the engineered molecules for three individual proteins - serotonin, lactate and TNT. Hellinga's success in creating a high specificity between the engineered protein and its ligand-the molecule to which it binds - portends great advances in biomedical technology.

Using a computer program that can recognize amino acid protein sequences through a process known as dead end elimination or computation, Hellinga's laboratory designed and created specialized proteins. Researchers then tested three model proteins to sense serotonin, lactate and TNT, respectively.

"[The computer program] knows how to describe atomic interactions.... It is very cleverly able to rule out combinations [of amino acids] which should not exist in dead end elimination," Hellinga said.

The implications of this research are wide, Hellinga added. The serotonin-sensing protein could aid doctors in understanding the effects that serotonin levels and electrical brain circuits have in an array of psychiatric disorders, while the lactate-sensing protein could signal metabolic stress in a living system.

"Such work is indeed exciting and should offer some exciting fruit by combining the best of genetic and computational approaches," said Scott Fraser, who is familar with the study and is a researcher at the California Institute of Technology, another university investigating dead end elimination.

Loren Looger, a graduate student who assisted in the research at Duke, said the TNT-sensing protein could be used to detect underwater explosives with greater accuracy and precision than currently available technology.

Looger said this protein research offers a way to monitor and "paint a nice profile" of a number of drugs and toxins in patients.

"I think the highly specific nature of our detection method (and the ability to develop sensors for most any compound) would be a significant contribution to medical monitoring," Looger wrote in an e-mail.

Duke is one of the few research facilities taking part in the study of these new engineered proteins. The other facilities currently researching the dead end elimination method include a facility in Germany and one at the University of Washington. Hellinga was the first to publish his findings.

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