Pharmacophore similarity scoring

Pharmacophore similarity scoring schemes are represented by the FBPA and ComPharm overlay dissimilarity scores, the expectation being to see low dissimilarity scores matching high activity levels. 

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. 

However, hypothesis models did clearly outperform similarity-based scoring with respect to the entire set. This advantage does not, as previously shown, stem from a better prediction of the subtle differences between the actives and inactives within the pharmacophoric Activity Zone . It may be ascribed to the ability of hypothesis models to correctly recognize actives that hide the key elements asked for by the model within a globally different pharmacophore pattern, which prevents them from being top ranked by the similarity search. 

Fig. 15.25 Partial display of virtual screen of conformational ensemble of " 75 000 structure library based on multiple templates. A display of fitness scores to a three-point pharmacophore model provides initial signs of similarity of a library design to that model. Subsequent virtual screening against a more stringent four-point pharmacophore model further highlights potentially useful library designs.

---