Protein-ligand interactions targets

Methods that utilize structural data of the target, generally identified by protein crystallography, to look for molecules that complement the binding site through favorable protein-ligand interactions (protein structure-based VS or SBVS). 

Once a suitable matrix is obtained, with the ligand coupled to it, and properly characterized with regard to ligand concentration, the effectiveness of the protein-ligand interaction can be evaluated. A sample containing the target protein is applied to the column, which is washed and evaluated for retained protein. 

In the last few years, a number of publications have demonstrated that the GRID/PCA or GRID/CPCA methods can be successfully applied to characterize the structural differences between protein binding sites, and to identify differences in the protein-ligand interactions as well as the regions on the target enzymes which mediate highly selective interactions [4—17]. 

Naumann and Matter used a set of 26 X-ray structures of eukaryotic protein kinases, which were classified into subfamilies with similar protein-ligand interactions in the ATP binding site. As can be seen in Fig. 3.13, which shows the GPGA score plot, PC 1 separates CDK and MAP/receptor kinases on the left from the family of PKA kinases. The CDK family is represented by two distinct clusters in the target family landscape, formed by two different ATP binding site conformations. They correspond to the activated and inactivated kinase conformations... 

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