In vitro selection of nucleic acids and proteins: What are we learning?

For almost a decade, in vitro selection experiments have been used to isolate novel nucleic acids, peptides and proteins according to their function. Selection experiments have altered our perception of molecular mimicry and catalysis, and they appear to be more facile than rational design at generating biopolymers with desired properties. New methods that have been developed improve the power of functional strategies in ways that nature has already discovered - by expanding library size and facilitating the recombination of positive mutations. Recent structural information on a number of selected and evolved molecules highlights future challenges for design via rational approaches.