Simple Models of the Protein Folding Problem

TL;DR

This paper explores the designability principle in protein folding, showing that highly designable structures are more stable, fold faster, and resemble natural protein motifs, providing insights into the selection of protein structures.

Contribution

It introduces the concept of designability in simplified protein models and links it to stability, foldability, and natural selection of protein structures.

Findings

Highly designable structures have more sequences associated with them.

These structures exhibit protein-like secondary motifs.

Highly designable structures are more thermodynamically stable and fold faster.

Abstract

The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I will give an introduction to the problem, and then focus on some recent work concerning the so-called ``designability principle''. The designability of a structure is measured by the number of sequences that have that structure as their unique ground state. Structures differ drastically in terms of their designability; highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures 1) possess ``proteinlike'' secondary structures and motifs, 2) are thermodynamically more stable, and 3) fold faster than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such selection simultaneously leads to thermodynamic stability and foldability. According to this picture, a key to the protein folding problem is to understand the emergence and the properties of the highly designable structures.