On the linkage of thermodynamics and pathogenicity

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.

Automated summary

This review provides an overview of how disease-causing mutations affect the thermodynamics of proteins. It focuses on the folding and binding free energy changes, which are crucial for structural integrity. The review highlights that complex diseases may result from mutations in multiple genes, while monogenic diseases are caused by mutations in a single gene. However, in both cases, pathogenic mutations have a greater impact on the thermodynamics compared to benign mutations. Recent studies investigating the effect of pathogenic mutations on thermodynamics, as well as structural dynamics and allosteric pathways, are discussed in the review.