NMR-based determination of the 3D structure of the ligand-protein interaction site without protein resonance assignment.
 

NMR-based determination of the 3D structure of the ligand-protein interaction site without protein resonance assignment.

NMR-based determination of the 3D structure of the ligand-protein interaction site without protein resonance assignment.

J Am Chem Soc. 2016 Mar 4;

Authors: Orts J, Wälti MA, Marsh M, Vera L, Gossert AD, Güntert P, Riek R

Abstract
Molecular replacement in X-ray crystallography is the prime method for establishing structure-activity relationships of pharmaceutically relevant molecules. Such an approach is not available for NMR. Here, we establish a comparable method, called NMR molecular replacement (NMR2). The method requires experimentally measured ligand intra-molecular NOEs and ligand-protein inter-molecular NOEs as well as a previously known receptor structure or model. Our findings demonstrate that NMR2 may open a new avenue for the fast and robust determination of the interaction site of ligand-protein complex- es at atomic resolution.


PMID: 26943491 [PubMed - as supplied by publisher]



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