Mapping out the Hydration Layer "Fingerprint" with Overhauser Dynamic Nuclear Polarization

A common mental model for biological macromolecules represents proteins as secondary structural elements with side-chains whose interactions are motivated by a combination of charge, hydrophobicity, and spatial fit (i.e. sterics and so-called "lock and key" mechanisms). This powerful model has yielded many important modern-day results. However, macromolecules are dramatically multi-dimensional systems and therefore exhibit interactions and motions governed not by intuitive potentials operating under spatial constraints, but by free energy. This is nowhere more apparent than when considering the layers of water and/or lipids that coat protein surfaces. Different patches of this "hydration layer" can display dramatically different enthalpies and entropies -- resulting in measurably different translational and rotational mobilities.

In this talk we explore how Electron Spin Resonance (ESR), Overhauser Effect Dynamic Nuclear Polarization (ODNP), and deuterium NMR can explore meaningful variations in the structure of the hydration layer and (in the case of trans-membrane proteins) the surfactant layer. A range of measurements on different systems (tranmembrane protein, vs. globular protein, vs. nanoconfined water) will be presented, as well as the long-term outlook on how such measurements might ultimately aid in understanding protein structure and binding events.