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.