(1988 Regan & DeGrado) A first success in de novo protein design

Reports the first design and biosynthesis of a protein with a sequence unlike any found in nature. The resulting structure, a four-helix bundle protein, was extraordinarily stable. Its design relied on a simple, repetitive structure and gave no detailed attention to the packing of internal side-chains. Subsequent studies showed that its internal structure was ill-defined (a so-called “molten globule” state). Later designs focused on the packing of internal side chains and produced proteins with stable, well-defined internal structures.