Structure determination of protein-ligand complexes by NMR in solution
- Author(s)
- Julien Orts, Alvar D. Gossert
- Abstract
In this paper, we discuss methods for determining structures of protein-ligand complexes by NMR in solution. Our discussion is based on small ligands (<2 kDa) as for example drugs, metabolites or oligo-peptides, but most of the considerations also apply to more general cases. In NMR in solution, the kinetics of association and dissociation of the complex – the exchange rate – determines the optimal sample preparation and the NMR experimental approach. Additionally, depending on the part of the complex that will be studied (only the bound ligand, the protein, the protein-ligand interface or the entire protein-ligand complex structure), different types of NMR experiments are needed. Therefore, the choice of a combination of the appropriate experiment and a suitable sample preparation in terms of ligand to protein ratios are discussed in detail. Also, considerations for practically preparing samples of protein-ligand complexes and carrying out experiments including trouble shooting are described. For structure determination, the scope of this paper is limited to NOE-based methods and some of the most recent approaches will be covered.
- Organisation(s)
- External organisation(s)
- Eidgenössische Technische Hochschule Zürich
- Journal
- Methods
- Volume
- 138-139
- Pages
- 3-25
- No. of pages
- 23
- ISSN
- 1046-2023
- DOI
- https://doi.org/10.1016/j.ymeth.2018.01.019
- Publication date
- 04-2018
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106006 Biophysics, 106002 Biochemistry
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all), Molecular Biology
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/structure-determination-of-proteinligand-complexes-by-nmr-in-solution(df0290ff-b96a-41f7-8616-7e7f59f40ae7).html