Alignment of weakly interacting molecules to protein surfaces using simulations of chemical shift perturbations

Structural studies of protein-ligand complexes are often limited by low sol ubility, poor affinity, and interfacial motion and, in NMR structures, by t he lack of intermolecular NOEs. In the absence of other structural restrain ts, we use a procedure that compares simulated chemical shift perturbations to observed perturbations to better define the binding orientation of liga nds with respect to protein surfaces.