Structural biology by NMR: structure, dynamics, and interactions

Abstract

The function of bio-macromolecules is determined by both their 3D structure and conformational dynamics. These molecules are inherently flexible systems displaying a broad range of dynamics on time-scales from picoseconds to seconds. Nuclear Magnetic Resonance (NMR) spectroscopy has emerged as the method of choice for studying both protein structure and dynamics in solution. Typically, NMR experiments are sensitive both to structural features and to dynamics, and hence the measured data contain information on both. Despite major progress in both experimental approaches and computational methods, obtaining a consistent view of structure and dynamics from experimental NMR data remains a challenge. Molecular dynamics simulations have emerged as an indispensable tool in the analysis of NMR data.

Figure 1. Illustration of structural data that can be obtained from NMR experiments, with the example of a backbone NH group.

Dashed line: short inter-proton distances based on NOE measurements; arrow: torsion angle from scalar couplings (J); heavy line: orientation of a bond vector in a coordinate frame rigidly attached to the molecule from residual dipolar couplings (D).

Figure 2. Time-scales, molecular motions (first panel), NMR experiments (second panel), and NMR parameters (bottom panel).

Molecular motions at a particular time-scale can be probed by analysing the NMR observables in the bottom panel by using the appropriate NMR experiments (see text). Indicated are the extreme cases, folding/unfolding (which can be observed with hydrogen exchange saturation via the chemical shift) and fast local dynamics (observed with spin relaxation experiments through measurements of the relaxation times T ₁, T ₂, and the NOE between the amide nitrogen and the amide proton). The cone indicates, in a qualitative way, the spatial extension of the motion described by the N-H group.