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How Much NMR Data Is Required To Determine a Protein–Ligand Complex Structure?
Author(s) -
Schieborr Ulrich,
Vogtherr Martin,
Elshorst Bettina,
Betz Marco,
Grimme Susanne,
Pescatore Barbara,
Langer Thomas,
Saxena Krishna,
Schwalbe Harald
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200500092
Subject(s) - ligand (biochemistry) , chemistry , intermolecular force , chemical shift , protein ligand , docking (animal) , biological system , experimental data , protein structure , ligand efficiency , nuclear magnetic resonance spectroscopy , computational chemistry , chemical physics , molecule , stereochemistry , mathematics , biochemistry , biology , statistics , organic chemistry , medicine , receptor , nursing
Here we present an NMR‐based approach to solving protein–ligand structures. The procedure is guided by biophysical, biochemical, or knowledge‐based data. The structures are mainly derived from ligand‐induced chemical‐shift perturbations (CSP) induced in the resonances of the protein and ligand‐detected saturated transfer difference signals between ligands and selectively labeled proteins (SOS‐NMR). Accuracy, as judged by comparison with X‐ray results, depends on the nature and completeness of the experimental data. An experimental protocol is proposed that starts with calculations that make use of readily available chemical‐shift perturbations as experimental constraints. If necessary, more sophisticated experimental results have to be added to improve the accuracy of the protein–ligand complex structure. The criteria for evaluation and selection of meaningful complex structures are discussed. These are exemplified for three complexes, and we show that the approach bridges the gap between theoretical docking approaches and complex NMR schemes for determining protein–ligand complexes; especially for relatively weak binders that do not lead to intermolecular NOEs.