Stability of Designed Proteins Against Mutations

TL;DR

This paper investigates the stability and designability of model proteins with designed sequences by enumerating sequences with mutations that still fold into the native structure, revealing high stability and a large number of foldable variants.

Contribution

It provides a comprehensive enumeration of mutated sequences that preserve folding, demonstrating the robustness and high designability of designed proteins.

Findings

Approximately 10^8-10^9 sequences fold into the native conformation.

Proteins with designed sequences show remarkable stability.

High designability indicates robustness to mutations.

Abstract

The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the total number of sequences obtained by introducing up to 4 point mutations and up to 7 composition--conserving mutations (swapping of amino acids) in a 36mers chain, it is found that there are $10^8-10^9$ sequences which in the folding process target onto the ``native'' conformation. Consequently, proteins with designed sequences display a remarkable degree of stability and, to a large extent, of designability.