1. Rapid protein-ligand costructures from sparse NOE data
- Author
-
Nico A. J. van Nuland, Gregg Siegal, Dipen M. Shah, Eiso Ab, Mathias A. S. Hass, and Tammo Diercks
- Subjects
Adenosine Triphosphatases ,Drug discovery ,Ligand ,Chemistry ,Intermolecular force ,Small molecule ligand ,Proteins ,Ligands ,Crystallography ,Drug Discovery ,Molecular Medicine ,HSP90 Heat-Shock Proteins ,Binding site ,Nuclear Magnetic Resonance, Biomolecular ,Protein ligand - 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.
- Published
- 2012