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Scientists program proteins to pair exactly

While the Ohio State Buckeyes and Washington Huskies prepared to butt heads in the Rose Bowl on Jan. 1, researchers at the two universities collaborated to create proteins that zip together in much the same way DNA molecules zip up to form a double helix.

The first-of-its-kind scientific breakthrough could enable the development of protein nanomachines that could help diagnose and treat disease, allow for more exact engineering of cells and perform a wide variety of other tasks.

Image courtesy University of Washington Institute for Protein Design

“This technique makes it possible for you to design proteins so they come together exactly how you want them to,” said Zibo Chen, a graduate student at the University of Washington and lead author of the paper, which was published Dec. 19 in the journal Nature.

The research heavily relied on the technical expertise of Ohio State’s Resource for Native Mass Spectrometry Guided Structural Biology, an NIH-funded center led by Vicki Wysocki, professor of chemistry and biochemistry and Ohio Eminent Scholar.

“Our contribution was the analysis of protein designs to confirm they were pairing correctly,” said Florian Busch, an Ohio State biochemist at the Resource for Native Mass Spectrometry and an author on the paper. “We also co-evolved with the ongoing project and came up with methods to analyze the designs faster and in mixtures that allowed proteins to find their correct partners even in the presence of other similar proteins.”

Typically, researchers interested in designing biomolecular nanomachines use DNA as the primary component, since complementary DNA strands come together in a highly predictable manner determined by base-pairing. The team developed protein designs that produce complementary proteins that precisely pair with each other by a similar approach, Busch explained.