Rapid protein-ligand costructures from sparse NOE data.

TitleRapid protein-ligand costructures from sparse NOE data.
Publication TypeJournal Article
Year of Publication2012
AuthorsShah, D. M., E. A. B, T. Diercks, M. A. S. Hass, N. A. J. van Nuland, and G. Siegal
JournalJ Med Chem
Volume55
Issue23
Pagination10786-90
Date Published2012 Dec 13
ISSN1520-4804
KeywordsAdenosine Triphosphatases, HSP90 Heat-Shock Proteins, Ligands, Nuclear Magnetic Resonance, Biomolecular, Proteins
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.

DOI10.1021/jm301396d
Alternate JournalJ. Med. Chem.
PubMed ID23145792