Molecular diversity in engineered protein libraries

Engineered protein libraries, defined here as a collection of different mutant variants of a single specific protein, are intentionally designed to be rich in molecular diversity and can span ranges from as little as 400 different variants to greater than 1012 members per library. The goal of engineering libraries is to generate new protein variants, identified upon screening, that possess desired novel properties. Exploitation of the natural organization of the genetic code has led to ‘focused’ libraries that are lower in overall complexity yet biased towards variants with preferred biophysical properties. An emerging trend, in which computational algorithms are blended with in vivo screens, is also leading towards greater and more rapid success in the field of protein design.