Ligand-Orientation Based Fragment Selection in STD NMR Screening.
While saturation transfer difference (STD) is a widely used NMR method for ligand screening, the selection of specific binders requires the validation of the hits through competition experiments or orthogonal biophysical techniques. We show here that the quantitative STD analysis is a reliable and robust approach to discriminate between specific and nonspecific ligands, allowing selection of fragments that bind proteins with a privileged binding mode, in the absence of any structural data for the protein.
Institut des Sciences Analytiques, UMR5280 CNRS, Université Lyon 1, Ecole Nationale Supérieure de Lyon, Université de Lyon , 5 rue de la Doua Villeurbanne 69100, France.
Olivier
O
Cala
Institut des Sciences Analytiques, UMR5280 CNRS, Université Lyon 1, Ecole Nationale Supérieure de Lyon, Université de Lyon , 5 rue de la Doua Villeurbanne 69100, France.
Isabelle
I
Krimm
D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries