Receptor similarity matrices

DISCO considers three-dimensional conformations of compounds not as coordinates but as sets of interpoint distances, an approach similar to a distance geometry conformational search. Points are calculated between the coordinates of heavy atoms labeled with interaction functions such as HBD, HBA or hydrophobes. One atom can carry more than one label. The atom types are considered as far as they determine which interaction type the respective atom would be engaged in. The points of the hypothetical locations of the interaction counterparts in the receptor macromolecule also participate in the distance matrix. These are calculated from the idealized projections of the lone pairs of participating heavy atoms or H-bond forming hydrogens. The hydrophobic points are handled in a way that the hydrophobic matches are limited to, e.g., only one atom in a hydrophobic chain and there is a differentiation between aliphatic and aromatic hydrophobes. A minimum constraint on pharmacophore point of a certain type can be set, e.g. if a certain feature is known to be required for activity [53, 54]. 

In the primate brain, a high concentration of the D4 receptor was detected in the cerebral cortex, hippocampus, thalamic reticular nucleus, GP and SNr (Mrzljak et al., 1996). Similar to rodents, in the primate striatum the D4 receptor appears to be more abundant in striosomes than matrix (Rivera et al., 2002b). 

Fig. 4. Similarity/identity matrix generated for chemotaxis and non-chemotaxis GPCRs. Matrix was prepared for a representative set of 23 chemotaxis receptors, as well as for rhodopsin and the OiB-adrenergic receptor, using the program MATGAT (Gampanella et al, 2003). The lower half of the matrix indicates overall sequence similarity between each pair of receptors, while the upper half indicates overall sequence identity.

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