Determination of protein–ligand binding modes using fast multi-dimensional NMR with hyperpolarization

Abstract

H] chemical shift correlations that contain intermolecular nuclear Overhauser effect (NOE) information. A scoring function based on this data is used to select pre-docked ligand poses. The top five poses are within 0.76 Å root-mean-square deviation from a reference structure for the encoded five protons, showing improvements compared with the poses selected by an energy-based scoring function without experimental inputs. The sensitivity enhancement provided by the D-DNP combined with multi-dimensional NMR increases the speed and potentially the selectivity of structure elucidation of ligand binding epitopes.

Topics & Concepts