The field of computational protein design is reaching its adolescence. Prot
ein design algorithms have been applied to design or engineer proteins that
fold, fold faster, catalyze, catalyze faster, signal, and adopt preferred
conformational states. Further developments of scoring functions, sampling
strategies, and optimization methods will expand the range of applicability
of computational protein design to larger and more varied systems, with gr
eater incidence of success. Developments in this field are beginning to hav
e significant impact on biotechnology and chemical biology.