Potential pharmacophoric points

Figure 13.3 Potential pharmacophore points can be generated with MOE s site detection algorithm. The white and red dots are the antomatically generated site points, and the ligand structure comes from the X-ray structure of the complex. See color plate.

Bottom Pharmacophore models calculated with different cluster radii from the aligned COX-2 inhibitors. The cluster radii of the four shown models are 1.0 A, 1.5 A, 3.0 A, and 3.5 A. The colored spheres represent potential pharmacophore points (PPP) of the models. The radii of the spheres denote the standard deviations of the spatial distributions of the atoms contributing to each PPP. Yellow hydrophobic interactions, magenta H-bond donors, cyan H-bond acceptors. Color intensity denotes the extent of conservation ofthe PPP among the aligned molecules (courtesy S. Renner). 

Moreover, geometric atom pairs and geometric binding property pairs were proposed, substituting the topological distance between two atom types with the - geometric distance [Sheridan et a/., 1996]. PPP-pairs are a particular case of geometric atom pairs where only pairs of the five potential pharmacophore points are considered [Brown and Martin, 1996]. 

Potential Pharmacophore Point pairs —> substructure descriptors ( pharmacophore-based descriptors)... 

Binding property torsions (bt) are binary descriptors for the presence/absence ofTinear sequences of four interconnected non-hydrogen atoms. These descriptors were proposed as an extension of topological torsions by assigning atoms to seven different types of potential pharmacophore points cations, anions, neutral hydrogen-bond donors and acceptors, polar atoms (both donor and acceptor, e.g., hydroxyl oxygen), and hydrophobic atoms and others [Kearsley, Sallamack et al, 1996]. 

Table S21 Potential pharmacophore point types from [Chen, Rusinko III et at. 1998].

Potential Pharmacophore Point keys (or 4-PPP keys) are binary string representations of molecules, which extend the concept of PPP triangle to combinations of four pharmacophore point types, that is, 4-point pharmacophores [Mason, Morize et al., 1999]. 

ALADDIN (91). DISCO uses a rapid technique, clique detection, to identify maps from the set of all potential pharmacophore points. Typically, the maps are generated in a few minutes of CPU time and the results can be viewed in a variety of molecular modeling programs. 

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