Tools for fragment based drug discovery

Binding Site Location

< Competition BindingBinding Orientation >

BINDING SITE LOCATION


The simplest, fastest and lowest cost method is based on mapping changes (Chemical Shift Perturbations or CSPs) in the HSQC spectrum (A) onto the known structure of the target. Where the sequential assignment is available, the CSPs can be mapped to the 3D structure of the target to define a low resolution binding site, as shown for MDM4. HSQC NMR spectra of proteins are highly sensitive to ligand binding. Therefore, this orthogonal technique can be used to validate and quantify binding of fragment hits to the target (B).

 

CSP


< Competition BindingBinding Orientation >