Ligand-target interaction data

Box 21.2 Representative Public Sources of Ligand-target Interaction Data... 

Chapter 14 in Section IV describes a workflow for designing a kinase targeted library. It illustrates how to assemble a lead generation library for a target family using known ligand-target family interaction data from various sources. 

The X data matrix which contains all information describing the probe-target interactions can be analyzed by PCA [29, 30]. PCA is a multivariate projection method which allows one to extract the systematic information which is contained in the data matrix and to present it in a simplified form. The original number of variables is reduced to a few factors called principal components (PCs). The result of such an analysis can then be visualized by means of two informative plots which allow a straightforward interpretation of the problem. In this way, PCA provides an understanding of similarities and dissimilarities between the different protein binding sites with respect to their interaction with potential ligands. 

The score matrix gives a simplified picture of the objects (probe-target interactions), represented by only a few, uncorrelated new variables (the PCs). Score plots, i.e. plots of the score vectors against each other, are a summary of the relationships between the objects and reveal the essential data patterns of the objects. Thus, objects which behave similarly have similar scores and are close in the score plot. In our context, score plots can be used to identify clusters of objects according to the different kind of targets (macromolecules) and probes (ligand chemical groups) involved. 

In this article, some examples are shown of the application of NMR spectroscopy in chemical biology. We put emphasis on experiments that characterize interactions of proteins and small molecular weight ligands. These interactions can be mapped either by characterizing the target protein (protein-observed experiments) or the ligand (ligand-observed experiments). Finally, the method of structure calculation based on NMR-derived data is briefly introduced. 

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). 

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