10.1021/jacs.5b12391.s001 Julien Orts Julien Orts Marielle Aulikki Wälti Marielle Aulikki Wälti May Marsh May Marsh Laura Vera Laura Vera Alvar D. Gossert Alvar D. Gossert Peter Güntert Peter Güntert Roland Riek Roland Riek NMR-Based Determination of the 3D Structure of the Ligand–Protein Interaction Site without Protein Resonance Assignment American Chemical Society 2016 NMR 2 receptor structure ligand intramolecular NOEs Protein Resonance Assignment Molecular replacement 3 D Structure method interaction site 2016-03-04 00:00:00 Dataset https://acs.figshare.com/articles/dataset/NMR_Based_Determination_of_the_3D_Structure_of_the_Ligand_Protein_Interaction_Site_without_Protein_Resonance_Assignment/3122401 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 (<i>N</i>MR<sup>2</sup>). The method requires experimentally measured ligand intramolecular NOEs and ligand–protein intermolecular NOEs as well as a previously known receptor structure or model. Our findings demonstrate that <i>N</i>MR<sup>2</sup> may open a new avenue for the fast and robust determination of the interaction site of ligand–protein complexes at atomic resolution.