Pucci Fabrizio, Rooman Marianne
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
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.
Philos Trans A Math Phys Eng Sci. 2016 Nov 13;374(2080). doi: 10.1098/rsta.2016.0141.
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'.
尽管在过去几十年里人们付出了巨大努力来理解蛋白质的热稳定性，但其调节机制仍存在争议。在本研究中，我们通过展示多尺度视角如何能产生新的见解来解决这个问题。借助温度依赖性统计势，我们在分子水平上分析了一些氨基酸相互作用，这些相互作用被认为与热抗性的增强有关。然后，我们通过量化氨基酸替换后蛋白质的修饰情况来研究蛋白质水平的热稳定性。最后，在结构组水平上对蛋白质稳定性进行大规模分析，有助于阐明稳定性与自然进化之间的关系，从而表明蛋白质的突变谱根据其热性质而有所不同。本文还简要讨论了多尺度方法如何有助于揭示蛋白质稳定性机制。本文是主题为“物理 - 化学 - 生物学界面的多尺度建模”特刊的一部分。
