Artificial proteins from combinatorial approaches.

How do we create new artificial proteins? In this review, we present a range of experimental approaches based on combinatorial and directed evolution methods used to explore sequence space and recreate structured or active proteins. These approaches can help to understand constraints of natural evolution and can lead to new useful proteins. Strategies such as binary patterning or modular assembly can efficiently speed structural and functional innovation. Many natural protein architectures are symmetric or repeated and presumably have emerged by coalescence of simpler fragments. This process can be experimentally reproduced; a range of artificial proteins obtained from idealized fragments has recently been described and some of these have already found direct applications.