Proteins Evolution Upon Point Mutations

TL;DR

This paper investigates how point mutations affect protein stability and evolvability, using classical concepts to understand the relationship between mutations, stability changes, and protein evolution.

Contribution

It demonstrates that protein stability changes from point mutations can predict evolutionary dynamics without explicitly considering epistasis effects.

Findings

Protein stability change upon mutations informs evolution via Boltzmann factors.

Mutations influence the ensemble of protein conformations and folding propensity.

Findings highlight the role of stability in the emergence of new protein functions.

Abstract

The primary aim of this work is to explore how proteins point mutations impact their marginal stability and, hence, their evolvability. With this purpose, we show that the use of four classic notions, namely, those from Leibniz & Kant (1768), Maynard Smith (1970), Einstein & Infeld (1961), and Anfinsen (1973), is sufficient for a better understanding of the protein-evolution and, consequently, to determine the factors that could control it. The preliminary results -- without considering epistasis effects explicitly -- indicate that the protein marginal-stability change upon point mutations provides the necessary and sufficient information to describe, through a Boltzmann factor, the evolution of the amide hydrogen-exchange protection factors. This finding is of paramount importance because it illustrates the impact of point mutations on both the protein marginal-stability and the ensemble of folded conformations coexisting with the native state and, in the presence of metamorphism, on the propensity for the appearance of new folds and functions.