Crystallography‐Independent Determination of Ligand Binding Modes

Abstract

Pass the spin: The internuclear NOE interactions for pharmacophore mapping (INPHARMA) can be used to derive the structure of receptor/ligand complexes for low-affinity lead compounds identified in the early stages of drug discovery. The relative binding mode and, in favorable cases, the absolute binding mode of pairs of competitive low-affinity ligands can be identified with INPHARMA. This is demonstrated for a system comprising protein kinase A (T in the schematic representation) and two activity inhibitors with known structures (LA and LB).