Why Do Proteins Look Like Proteins?

TL;DR

This paper uses a lattice model to show that highly designable and stable protein-like structures naturally emerge, explaining the regularity and symmetry observed in real proteins due to evolutionary selection for designability and stability.

Contribution

It demonstrates that structural regularities in proteins are linked to high designability and stability, providing a simple model explanation for protein structure evolution.

Findings

Highly designable structures have many associated sequences.

Such structures exhibit secondary structures and symmetries.

They are thermodynamically more stable than less designable structures.

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.