3.6.1. DIRECTION
One of the methods called difference of inversion recovery rate with and without target irradiation (DIRECTION) is used to map pharmacophores and can be an alternative to STD experiments. This method uses the difference between longitudinal relaxation rates of ligand protons with- and with-out irradiation of the protons of the target protein. The DIRECTION approach, however cannot be used for slowly exchanging (strong binding) ligands. The practical approach of this method was demonstrated on the experiment when analyzed the interactions between p38 MAPK (p38 a mitogen-activated protein kinase) and its inhibitor-SB203580 [389,390]. The results from this experiment showed that protons H1, H4, H5, and H6 of SB203580, are in close neighborhood with the protons of p38 MAPK when compared with H2, H3, and methyl protons. It indicates that two aromatic rings (a pyridine ring and fluorophenyl ring) of SB203580 interact tightly with p38 MAPK. The results were later confirmed with proton density map of each ligand’s proton, based on the crystal structure of SB203580–p38 MAPK complex [391]. Moreover, the same authors already created a new and improved protein–ligand docking method by combining the DIRECTION obtained NMR data with docking software. [392].