We just created 'impossible' proteins that work perfectly even though they're missing the 'essential' shape science said they needed.
April 17, 2026
Original Paper
De novo acyl carrier proteins display structure-independent modification and sequence novelty
bioRxiv · 2025.06.07.658270
The Takeaway
One of the first things you learn in biology is that a protein's 3D shape (its 'fold') determines everything it does. Scientists decided to test this by designing synthetic proteins that completely lacked the standard shape everyone thought was required for them to function. To their shock, the enzymes that modify these proteins didn't care at all—they recognized and worked on these shapeless proteins just as well as the natural ones. This proves that for some of the most fundamental processes in life, the 'lock and key' model is a lot more flexible than we thought. It opens the door to creating a whole new class of 'designer' proteins that don't follow the rules of nature.
From the abstract
Acyl carrier proteins (ACPs) are dynamic, structurally conserved -helical proteins central to many primary and secondary metabolic processes. Whilst prior engineering efforts have focused on strategic mutagenesis and "helix swaps", much of the ACP sequence design space remains underexplored. Here, we create diverse variants of the archetypal ACP subclass - AcpP - using a bespoke sequence-generating algorithm (ALGO-CP), which utilises a combined evolutionary and physicochemical design approach. U