Making invisible excited-state structures of pro-interleukin-18 visible by combining NMR and machine learning
Abstract
NMR spectroscopy is a powerful tool for studies of protein dynamics over timescales extending more than twelve orders of magnitude, with motion queried at many of the backbone and sidechain positions in the molecule of interest. NMR experiments can, in principle, provide atomic resolution descriptions of excited conformational states that are sparsely populated and transiently formed-i.e., invisible, and there are examples of such structures in the literature. However, in other cases, the NMR data are not sufficient for generating structural ensembles of rare and transient higher energy conformers of the protein of interest. One example is provided by the precursor form of the proinflammatory cytokine interleukin-18, pro-IL-18, studied here. Although NMR studies show that pro-IL-18 adopts two sparsely populated (
Fields of Study & Subjects
Inflammasome and immune disorders
Streptococcal Infections and Treatments
Tryptophan and brain disorders
Publication details
- Journal / source
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Volume
- 123
- Issue
- 16
- Pages
- e2537014123–e2537014123
- Publication date
- 17 April 2026
- Language
- EN