Advances in the exact nuclear Overhauser effect 2018-2022.

The introduction of the exact nuclear Overhauser enhancement (eNOE) methodology to solution-state nuclear magnetic resonance (NMR) spectroscopy results in tighter distance restraints from NOEs than in convention analysis. These improved restraints allow for higher resolution in structure calculation and even the disentanglement of different conformations of macromolecules. While initial work primarily focused on technical development of the eNOE, structural studies aimed at the elucidation of spatial sampling in proteins and nucleic acids were published in parallel prior to 2018. The period of 2018-2022 saw a continued series of technical innovation, but also major applications addressing biological questions. Here, we review both aspects, covering topics from the implementation of non-uniform sampling of NOESY buildups, novel pulse sequences, adaption of the eNOE to solid-state NMR, advances in eNOE data analysis, and innovations in structural ensemble calculation, to applications to protein, RNA, and DNA structure elucidation.