The Marginal Stability of Proteins: How Jiggling and Wiggling of Atoms are Connected to Neutral Evolution

TL;DR

This paper proposes that the universal upper bound on protein stability is a thermodynamic property, suggesting that neutral evolution is also a universal phenomenon related to protein stability, independent of molecular changes.

Contribution

It introduces the idea that protein stability's upper bound is a universal thermodynamic property, linking it to neutral evolution across molecular complexes.

Findings

Protein stability upper bound is approximately 7.4 kcal/mol.

This stability limit is unaffected by mutations or modifications.

The stability bound stems from thermodynamic principles, not evolutionary processes.

Abstract

Here we propose that the upper bound marginal stability of proteins (7.4 kcal/mol) is a universal property that includes macro-molecular complexes and is not affected by molecular changes such as mutations and Post-Translational Modifications. Its existence is, essentially, a consequence of the Anfinsen thermodynamic hypothesis rather than a result of an evolutive process. This result enables us to conjecture that neutral evolution should also be, with respect to protein stability, a universal phenomenon.