3.6.8. HECSP
In silico methods combined with NMR derived information can also be used to determine accurate drug-target complexes. 1H empirical chemical shift perturbation (HECSP) is an empirical model that is based on chemical shift perturbation (CSP) of a protein. CSP represents the change in chemical shifts in a protein due to alteration of its chemical environment (which can happen upon ligand binding). The CSP of a target protein is obtained by a series of 2D HSQC experiments with a set of ligand titrations involving samples that contain 15N-labelled protein. The calculation of 1H-CSPs inside the protein are based on four contributors: 1) ring current, 2) electric field, 3) hydrogen bonding, and last 4) magnetic anisotropy. To show the value of the HECSP model two CSP examples were used: apo-neocarzinostatin (apoNCS)-naphthoate ester complex, and human intestinal fatty acid binding protein (hIFABP)-ketorolac-ANS complex. The results from the experiment showed that HECSP model can distinguish native ligand from decoys and more clearly define protein-ligand complex structures with NMR derived information [407].