A new approach to the design of stable proteins

We propose a simple algorithm to design a sequence which fitsa given protein structure with a given energy. The algorithmis a modification of the Metropolis Monte Carlo scheme in sequencespace with an evolutionary temperature which sets the energyscale. There is a one to one correspondence between this optimizationscheme and the Ising model of ferromagnetism. This analogy impliesthat the design algorithm does not encounter multiple-minimaproblems and is very fast. The algorithm is tested by ‘predicting’the primary structures of four proteins. In each case the calculatedprimary structures had statistically significant homology withthe natural structures.