Fuzzy Pharmacophore Models

Top 3D alignment of COX-2 inhibitors 5, 6, and 7. Rofecoxib and M5 were aligned to the crystal structure conformation of SC-558 bound to COX-2. 

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). 

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Fig. 3.10 SQUID fuzzy pharmacophore model for COX-2 inhibitors. Using a larger cluster radius results in more general models. From left to right 1 A, 1.5 A, 2.5 A, 3.5 A.

Fig. 3.13 (a) SQUID fuzzy pharmacophore model of Tat-TAR interaction inhibitors, (b) Alignment of the best hit (colored by atom types) found with SQUID with the reference alignment (red, acetylpromazine green, fragment of CGP40336A). 

Tat-TAR RNA interaction found with a fuzzy pharmacophore model. ChemBioChem, 6, 1119-1125. 

Bonachera, F., Parent, B., Barbosa, F., Froloff, N., and Horvath, D. (2006) Fuzzy tricentric pharmacophore fingerprints. 1. Topological fuzzy pharmacophore triplets and adapted molecular similarity scoring schemes. Journal of Chemical Information and Modeling, 46, 2457-2477. 

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