Designing better membrane proteins by embracing imperfection

Scientists at the VIB–VUB Center for Structural Biology have uncovered a counterintuitive principle that could reshape how membrane proteins are designed from scratch: Sometimes, making a protein less stable helps it fold correctly. In their study published in the Proceedings of the National Academy of Sciences, the researchers demonstrate that introducing carefully placed "imperfections," a strategy known as negative design, enables synthetic membrane proteins to fold and assemble efficiently in artificial membranes.