NMR methods to dissect the molecular mechanisms of disease-related mutations (DRMs): Understanding how DRMs remodel functional free energy landscapes

Elucidating the molecular mechanism of disease-related mutations (DRMs) is a critical first step towards understanding the etiology of genetic disorders. DRMs often modulate biological function by altering the free-energy landscape (FEL) of the protein associated with the mutated gene. FELs typically include ground, as well as excited, yet accessible and functionally relevant, states and DRMs may perturb both the thermodynamics and kinetics of …