title: Improved insights into protein thermal stability: from the molecular to the structurome scale.
abstract: 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 temperature-dependent 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'.
authors.affiliation: Department of BioModeling, BioInformatics and BioProcesses, Université Libre de Bruxelles, CP 165/61, Roosevelt Avenue 50, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, CP 263, Triumph Boulevard, 1050 Brussels, Belgium fapucci@ulb.ac.be.
authors.forename: Fabrizio
authors.identifier: http://orcid.org/0000-0003-2916-022X
authors.initials: F
authors.lastname: Pucci
authors.affiliation: Department of BioModeling, BioInformatics and BioProcesses, Université Libre de Bruxelles, CP 165/61, Roosevelt Avenue 50, 1050 Brussels, Belgium Interuniversity Institute of Bioinformatics in Brussels, CP 263, Triumph Boulevard, 1050 Brussels, Belgium.
authors.forename: Marianne
authors.initials: M
authors.lastname: Rooman
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins
keywords: amino acid interactions; evolutionary pressure; protein mutations; stability prediction; statistical potentials