Figure 3. Plot of the design free energy surface for protein L7/L12 (PDB ID 1CTF) as a function of the total energy and the logarithm of the number of possible letter permutations .

For small values of the sequences will tend to be more and more homopolymeric. The most stable sequences corresponds to the to lowest free energy point (indicated by the the LowF arrow) and the folding capacity deteriorates moving away from that point even if the total energy is lower (e.g. the point indicated by the LowE arrow). The boundaries are determined by the limits in the computational power but also by the fact that some combinations of and are not possible.