Protein-fragment complex structures derived by NMR molecular replacement
- Author(s)
- Felix Torres, Dhiman Ghosh, Dean Strotz, Celestine N. Chi, Ben Davis, Julien Orts
- Abstract
Recently we have established an NMR molecular replacement method, which is capable of solving the structure of the interaction site of protein–ligand complexes in a fully automated manner. While the method was successfully applied for ligands with strong and weak binding affinities, including small molecules and peptides, its applicability on ligand fragments remains to be shown. Structures of fragment–protein complexes are more challenging for the method since fragments contain only few protons. Here we show a successful application of the NMR molecular replacement method in solving structures of complexes between three derivatives of a ligand fragment and the protein receptor PIN1. We anticipate that this approach will find a broad application in fragment-based lead discovery.
- Organisation(s)
- External organisation(s)
- Eidgenössische Technische Hochschule Zürich, Vernalis PLC
- Journal
- RSC Medicinal Chemistry
- Volume
- 11
- Pages
- 591-596
- No. of pages
- 6
- DOI
- https://doi.org/10.1039/d0md00068j
- Publication date
- 05-2020
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106006 Biophysics, 106002 Biochemistry
- Keywords
- ASJC Scopus subject areas
- Drug Discovery, Molecular Medicine, Biochemistry, Pharmacology, Pharmaceutical Science, Organic Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/88204bb4-b64a-460a-addb-046d9a4f195a