High-pressure NMR of Biological Systems in Solution

High-pressure is a well-known perturbation method that can be used to destabilize globular proteins and dissociate protein complexes. In addition, pressure perturbation is generally fully reversible, which is essential for a proper thermodynamic characterization of protein equilibrium when combined with NMR spectroscopy; pressure perturbation allows a detailed characterization of the factors governing the stability of globular proteins and their folding mechanisms. In this article, the author will present the thermodynamic aspects of pressure perturbation and contributions to the volume change upon unfolding. The author will also highlight the fundamental differences between pressure perturbation and chemical denaturation and present an overview of high-pressure NMR techniques used for the detection of low-lying excited states and characterization of protein folding mechanisms and kinetics.