A new approach to the design of stable proteins.

We propose a simple algorithm to design a sequence which fits a given protein structure with a given energy. The algorithm is a modification of the Metropolis Monte Carlo scheme in sequence space with an evolutionary temperature which sets the energy scale. There is a one to one correspondence between this optimization scheme and the Ising model of ferromagnetism. This analogy implies that the design algorithm does not encounter multiple-minima problems and is very fast. The algorithm is tested by 'predicting' the primary structures of four proteins. In each case the calculated primary structures had statistically significant homology with the natural structures.