The nuclear Overhauser effect from a quantitative perspective

The nuclear Overhauser enhancement or effect (NOE) is the most important measure in liquid-state NMR with macromolecules. Thus, the NOE is the subject of numerous reviews and books. Here, the NOE is revisited in light of our recently introduced measurements of exact nuclear Overhauser enhancements (eNOEs), which enabled the determination of multiple-state 3D protein structures. This review encompasses all relevant facets from the theoretical considerations to the use of eNOEs in multiple-state structure calculation. Important aspects include a detailed presentation of the relaxation theory relevant for the nuclear Overhauser effect, the estimation of the correction for spin diffusion, the experimental determination of the eNOEs, the conversion of eNOE rates into distances and validation of their quality, the distance-restraint classification and the protocols for calculation of structures and ensembles. (C) 2013 Elsevier B.V. All rights reserved.