  Biological diversity has evolved despite the essentially infinite complexity
of protein sequence space. We present a hierarchical approach to the efficient
searching of this space and quantify the evolutionary potential of our approach
with Monte Carlo simulations. These simulations demonstrate that non-homologous
juxtaposition of encoded structure is the rate-limiting step in the production
of new tertiary protein folds. Non-homologous ``swapping'' of low energy
secondary structures increased the binding constant of a simulated protein by
$\approx10^7$ relative to base substitution alone. Applications of our approach
include the generation of new protein folds and modeling the molecular
evolution of disease.
