title: Pose scoring by NMR.
abstract: 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.
authors.affiliation: 152 Davey Laboratory, Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Kaushik
authors.initials: K
authors.lastname: Raha
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Merz
mesh_terms: D001665:Binding Sites; D008024:Ligands; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D022061:Tacrolimus Binding Protein 1A / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: C104949:GPI 1046; D008024:Ligands; D011759:Pyrrolidines; D022061:Tacrolimus Binding Protein 1A