Why Do Proteins Look Like Proteins?

Abstract

Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural regularities are related to high designability and evolutionary stability. We measure the designability of each compact structure by the number of sequences which can design the structure, i.e., which possess the structure as their nondegenerate ground state. We find that compact structures are drastically different in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These structures are found to have ``protein like'' secondary structure and even tertiary symmetries. In addition, they are also thermodynamically more stable than ordinary structures. These results suggest that protein structures are selected because they are easy to design and stable against mutations, and that such a selection simutaneously leads to thermodynamic stability.