Proteins are the workhorses of cells, and scientists have long been able to tweak their structure to change how they bind to their molecular targets. But they’ve never managed to design their own proteins from scratch to bind to new small targets—until now.
Using a computer program to rapidly model such “designer” proteins, the team created 56 variations. Each had a barrellike shape with an internal cavity that could bind to small target molecules. In this case, the target was DFHBI, a molecule that fluoresces when bound. The researchers tweaked their best binders and came up with three designs that worked with even tiny amounts of DFHBI. When they added their synthetic proteins to cells with DFHBI (above), the cells lit up, they report today in Nature.
The approach paves the way to creating biosensors that can measure gene expression or track the presence of chemicals inside cells, including powerful narcotics like fentanyl. Those advances, scientists say, could give doctors a suite of new tools for diagnosing and treating dangerous diseases—and monitoring the effectiveness of medical treatments.