Improved insights into protein thermal stability: from the molecular to the structurome scale

Abstract

One contribution of 17 to a theme issue 'Multiscale modelling at the physics-chemistry-biology interface' . Despite the intense efforts of the last decades to understand the thermal stability of proteins, the mechanisms responsible for its modulation still remain debated. In this investigation, we tackle this issue by showing how a multiscale perspective can yield new insights. With the help of temperaturedependent statistical potentials, we analysed some amino acid interactions at the molecular level, which are suggested to be relevant for the enhancement of thermal resistance. We then investigated the thermal stability at the protein level by quantifying its modification upon amino acid substitutions. Finally, a large scale analysis of protein stability-at the structurome level-contributed to the clarification of the relation between stability and natural evolution, thereby showing that the mutational profile of proteins differs according to their thermal properties. Some considerations on how the multiscale approach could help in unravelling the protein stability mechanisms are briefly discussed.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

A meta-analysis of the activity, stability, and mutational characteristics of temperature-adapted enzymes

“…The average ΔT m was -2.06, -2.23 and -2.51 °C for psychrophiles, mesophiles and thermophiles respectively. The results suggest that the average reduction in the melting temperature of an enzyme upon mutation increases from psychrophiles to thermophiles, which agrees with previous literature [32]. The only Dunnett's T3 multiple comparisons test to produce a statistically significant result was between the psychrophiles and the thermophiles (p value = 0.0019).…”

Insights on protein thermal stability: a graph representation of molecular interactions

“…The ensemble comparison has two main purposes: The first consists in overcoming the limitation of the need of pairs of homologous proteins for direct comparison. The second purpose, raised from the observation that thermostable proteins are enriched of high connected nodes (hubs) and have more organized networks of interactions respect mesostable proteins (Jonsdottir et al , 2014; Kumar et al , 2000; Pucci and Rooman, 2016), relies in the need introducing a quantitative measure of the evolutionary optimization process thermostable proteins underwent, i.e. the distance between real protein interaction network and a randomized one, in which we disrupt the optimization of energy achieved by thermostable proteins during evolution.…”

Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting

“…1, E and F) (7). However, with a higher than 90% reversible thermal stability in the presence of a chaotrope (table S3), CMPX-152A is more thermostable than the average mesostable protein (T M of 54°C in the absence of GuHCl) (34).…”