Designability and Thermal Stability of Protein Structures

TL;DR

This paper reviews theoretical research indicating that certain protein folds are inherently more designable and thermally stable, which may explain the limited diversity of natural protein structures and aid in designing new ones.

Contribution

It highlights the concept of the designability principle, linking structural designability with thermal stability and suggesting its role in natural fold diversity and protein engineering.

Findings

Highly designable folds are low energy states for many sequences

Sequences for these folds tend to be thermally stable

The designability principle can guide new protein fold design

Abstract

Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of an unusually large number of sequences. The sequences associated with these folds are also found to be unusually thermally stable. The connection between highly designable structures and highly stable sequences is generally known as the "designability principle". The designability principle may help explain the small number of natural folds, and may also guide the design of new folds.