Overview of Relaxation Dispersion NMR Spectroscopy to Study Protein Dynamics and Protein-Ligand Interactions

Abstract

Proteins and nucleic acids are central to all biological processes. NMR spectroscopy has proven to be excellent for studying the dynamics of these macromolecules over various timescales. Relaxation rates and heteronuclear nuclear Overhauser‐effect values can resolve motion on pico‐ to nanosecond timescales, residual dipolar couplings provide information on submicro‐ to millisecond timescales, and even slower dynamics over seconds to hours can be resolved by hydrogen‐exchange experiments. Relaxation dispersion experiments are especially valuable because they resolve motion on micro‐ to millisecond timescales, encompassing biomolecular motions associated with ligand binding, enzymatic catalysis, and domain‐domain opening. These experiments provide structural, kinetic, and thermodynamic information on “invisible” excited conformational states. Relaxation dispersion can be applied not only to single biomolecules but also to protein‐ligand complexes to study the kinetics and thermodynamics of association and dissociation. We review recent developments in relaxation dispersion methodology, outline the R1ρ relaxation dispersion experiment, and discuss application to biomolecular interactions. © 2018 by John Wiley & Sons, Inc.