Evolutionary approaches for the discovery of functional synthetic small molecules

Directed evolution is a powerful method for the laboratory discovery of nucleic acids and proteins with desired functional properties. A hallmark of this approach is the iterative translation, selection, amplification, and diversification of genetic information. The potential of evolutionary methods to impact the discovery of synthetic small molecules has recently been explored by a variety of laboratories. Four methods encompassing some or all of the hallmarks of evolution are discussed, including dynamic combinatorial chemistry (DCC), genetic algorithms (GAs), DNA display, and DNA-templated synthesis (DTS).