title: Rapid protein-ligand costructures from sparse NOE data.
abstract: An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden 2300RA, The Netherlands.
authors.forename: Dipen M
authors.initials: DM
authors.lastname: Shah
authors.forename: Eiso
authors.initials: E
authors.lastname: A B
authors.forename: Tammo
authors.initials: T
authors.lastname: Diercks
authors.forename: Mathias A S
authors.initials: MA
authors.lastname: Hass
authors.forename: Nico A J
authors.initials: NA
authors.lastname: van Nuland
authors.forename: Gregg
authors.initials: G
authors.lastname: Siegal
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011506:Proteins / Q000737:chemistry*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D011506:Proteins; D000251:Adenosine Triphosphatases