Novel proteins: from fold to function

The field of de novo protein design, though only two decades old, has already reached the point where designing and selecting novel proteins that are functionally active has been achieved several times. Here we review recently reported de novo functional proteins that were developed using various approaches, including rational design, computational optimization, and selection from combinatorial libraries. The functions displayed by these proteins range from metal binding to enzymatic catalysis. Some were designed for specific applications in engineering and medicine, and others provide life-sustaining functions in vivo.

► We review recent advances on de novo proteins that are functionally active.
► Approaches for developing functional de novo proteins include rational design, computational optimization, and selection from combinatorial libraries.
► Functions range from metal-binding and catalysis to life-sustaining functions in vivo.
► Potential applications include nanotechnology, engineering, and medicine.