Synthetic biologists have taken evolution of proteins into their own hands by changing some that occur in nature or even by synthesizing them from scratch. Such engineered proteins are used as highly efficacious drugs, components of synthetic gene circuits that sense biological signals, or in the production of high-value chemicals in ways that are more effective and sustainable than petroleum-based methods. To engineer them, they use two very different approaches. In “directed evolution”, they randomly vary the linear sequence of amino acid building blocks encoding a natural protein and screen for variants with the desired activity; or they use “rational design” to model proteins based on their actual 3D structures to identify amino acids that likely will impact protein function. However, directed evolution can only cover a small part of the enormous space of possible protein sequences, while rational design approaches are limited by the relative scarcity of painstakingly resolved 3D protein structures.
