BIOBRIEF
A Washington University in St. Louis and Syracuse framework applies rational design to intrinsically disordered protein regions, which exist in roughly 70% of human proteins and are linked to cancer and neurodegeneration.
Researchers at Washington University School of Medicine in St. Louis and Syracuse University have published a peer-reviewed framework in Nature for rationally designing intrinsically disordered protein regions, the constantly rearranging stretches that make up roughly 70% of human proteins and have largely resisted engineering because they lack a stable 3D shape.
The framework, outlined in "Rational design of disordered proteins for sequence–function investigation," treats a protein's amino acid sequence as the designable object rather than a target structure. Folded-protein design has raced ahead in recent years, but IDR design stalled on the absence of structural templates. The new tool lets researchers specify a sequence to get a desired behavior in regions that constantly interconvert among many conformations.
"Our work uses rational sequence design as a powerful method for exploring function in IDRs and provides a versatile tool for designing functional disordered proteins," said Alex Holehouse, in remarks reported by Genetic Engineering & Biotechnology News.
The work, confirmed in a Washington University press release and an EurekAlert notice, has translational scope: IDRs are implicated in cancer and neurodegeneration. A bioRxiv preprint traces the project's earlier development.
The authors caution that the framework advances rather than solves sequence-to-function prediction for disordered proteins, keeping the contribution in the research-tool lane.