Mapping Protein Conformational Landscapes with High-Pressure NMR

This review focuses on the use of high-pressure nuclear magnetic resonance (HP NMR) to map local protein stability and conformational landscapes, with an emphasis on the population and characteristics of protein excited states. Section 1 discusses the volumetric properties of proteins in the pressure–temperature plane, highlighting the underlying mechanisms of pressure effects, the magnitude of the volume changes upon unfolding, their temperature dependence, and the nature of the unfolded state at high pressure. In Section 2, NMR-detected, pressure-induced equilibrium unfolding of proteins is discussed. Section 3 covers how HP NMR can reveal the complexity of protein conformational landscapes, the population of excited states, and the local stability distribution across the structure. Studies exploring the sequence determinants of these landscapes are presented. Of particular interest are the sequence determinants that define the excited states implicated in functional dynamics, one of the most important unresolved issues in protein science.