Design of proteins from smaller fragments-learning from evolution.

Nature has generated an impressive set of proteins with diverse folds and functions. It has been able to do so using mechanisms such as duplication and fusion as well as recombination of smaller protein fragments that serve as building blocks. These evolutionary mechanisms provide a template for the rational design of new proteins from fragments of existing proteins. Design by duplication and fusion has been explored for a number of symmetric protein folds, while design by rational recombination has just emerged. First experiments in recombining fragments from the same and different folds are proving successful in building new proteins that harbor easily evolvable properties originating from the parents. Overall, duplication and recombination of smaller fragments shows much potential for future applications in the design of proteins.