Pharmacophores centre types

When used for relative similarity and diversity, only potential pharmacophores that contain the defined special centre-type are used. The frame of reference for similarity/diversity studies is thus changed to one that is focused on the feature of interest distances are now measured relative to this special centre. For example, the special centre could be the centroid of a substructure [10] such as biphenyl tetrazole or diphenylmethane, enabling the calculation and comparison of all 3D pharmacophoric shapes that contain this substructure the substructure is said to be privileged . For structure-based design, the potential pharmacophores in a site can be restricted to those that contain a specific site point (e.g. in a pocket, or at the entrance to a pocket). In the context of combinatorial library design, the relative measure can be those pharmacophoric shapes that contain a special site-point that represents where the attachment point for a reagent would be. In figure 1, the special point would be centre-type number 3, which can be reserved for this purpose. 

The definition of the pharmacophore is important in order to obtain meaningful estimates of promiscuity and diversity. In Chem-X, the pharmacophore is defined in terms of the types of interaction with the receptor and the distance between the centres of these interactions. In the Jan98 release ofChem-X, 7 centre types were used ... 

Henkel et al. did not differentiate the natural products from natural product derivatives. The descriptors they used for comparison were molecular weight, number and type of hetero atoms, pharmacophore groups (e.g. CO, CONH, OH, CN, NH, etc), bridgehead atoms, rotatable C C bonds, rings per molecule, chiral centres per molecule and rotatable bonds per molecule. 

All systems offering rapid searching utilise 3-D keys, usually based on the distance between atoms. In ChemDBS-3D we base our keys on the generic properties of atoms that are important to pharmacophoric action these are termed centres. We currently use four types of centre hy default ... 

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