论热力学与发病机制的联系。
On the linkage of thermodynamics and pathogenicity.
机构信息
Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA.
Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA.
出版信息
Curr Opin Struct Biol. 2023 Jun;80:102572. doi: 10.1016/j.sbi.2023.102572. Epub 2023 Mar 23.
This review outlines the effect of disease-causing mutations on proteins' thermodynamics. Two major thermodynamics quantities, which are essential for structural integrity, the folding and binding free energy changes caused by missense mutations, are considered. It is emphasized that disease effects in case of complex diseases may originate from several mutations over several genes, while monogenic diseases are caused by mutation is a single gene. Nevertheless, in both cases it is shown that pathogenic mutations cause larger perturbations of the above-mentioned thermodynamics quantities as compared with the benign mutations. Recent works demonstrating the effect of pathogenic mutations on the above-mentioned thermodynamics quantities, as well as on structural dynamics and allosteric pathways, are reviewed.
这篇综述概述了致病突变对蛋白质热力学的影响。考虑了两个主要的热力学量，它们对于结构完整性至关重要，即错义突变引起的折叠和结合自由能变化。需要强调的是，在复杂疾病的情况下，疾病效应可能源于几个基因上的几个突变，而单基因疾病则是由单个基因突变引起的。然而，在这两种情况下，都表明致病突变会引起上述热力学量的更大扰动，而良性突变则不会。本文综述了最近的研究工作，这些研究工作表明了致病突变对上述热力学量以及结构动力学和变构途径的影响。
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