Pose scoring by NMR

Recently, we have developed a fast approach to calculate NMR chemical shifts using the divide and conquer method at the semiempirical level. To demonstrate the utility of this approach for characterizing protein-ligand interactions, we used the deviation of calculated chemical shift perturbations from experiment to determine the orientation of a ligand (GPI-1046) in the binding pocket of the FK506 binding protein (FKBP12). Moreover, we were able to select the native state of the ligand from a collection of decoy poses. A key hydrogen bond between O1 and HN in Ile56 was also identified. Our results suggest that ligand-induced chemical shift perturbations can be used to refine protein/ligand structures.