Virtual pharmacophore-based

Flohr S, Kurz M, Kostenis E, Brkovich A, Fournier A, Klabunde T. Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Ghent 2002 45 1799-805. 

Keywords VS, Virtual Screening, Lead discovery, lead, HTS, Pharmacophore-Based, Structure-Based, Fragment-based, Ligand-based, Docking, Scoring, hybrid workflows, VS strategy, Benchmarking VS... 

PF1BVS Pharmacophore-based virtual screening SBVS (Protein) Structure-based virtual screening... 

Fig. 4.1 Virtual screening tools can be categorized by the compound data to be screened (compound collection, combinatorial library, chemistry space) and the query type (structure-based, ligand-based, descriptor-based, pharmacophore-based). The output is always a list of compounds together with a score quantifying the fit to the query.

Pharmacophore mapping (pharmacophore-based virtual screening) given the relative orientation of a few functional groups in space (a pharmacophore), ligand molecules that are able to fulfill the pharmacophore are searched for. 

Catalyst was also used by Singh et al. for the identification of potent and novel integrin a4/Sl antagonists [294]. The authors describe a series of potent inhibitors of a4 81 that were discovered using pharmacophore-based virtual screening for replacements of the peptide region of an existing tetrapeptide-based inhibitor derived from fibronectin. 

Strengths and Limitations of Pharmacophore-Based Virtual Screening... 

I 5 Strengths and Limitations of Pharmacophore-Based Virtual Screening Tab. 5.2 The six-variable linear overlay-based Cox2 QSAR model... 

Sun, H. (2008) Pharmacophore-based virtual screening. Curr Med Chem 15, 1018-1024. 

Drie, J. H. (2005) Pharmacophore-based virtual screening a practical perspective, in (Alvarez, J., Shoichet, B., eds.) Virtual Screening in Drug Discovery. CRC Press, Boca Raton, FL, pp. 157-205. 

Virtual screening often benefits from an expert bias which helps focus on more desirable results, given in the form of additional information. A point in case is docking under pharmacophore constraints [37] or the concept of relative pharmacophores with a special internal reference point [38]. Yet another application for a directionally biased compound comparison is the selection of chemical reagents where functional attachment points are aligned and pharmacopho-ric features are examined relative to this point of reference by a procedure termed GaP [39]. Other concepts which try to describe combinatorial products in terms of their educts and need a special reference point are shape-based To-pomers [24] and pharmacophore based OsPreys [40]. 

In many cases, the performance of a pharmacophore-based virtual screen can be improved when the quality of the mapping to the respective pharmacophore is considered. Fit values of all test set molecules on to both pharmacophores can be calculated and the compounds can be sorted using the fit value of their mappings. The resulting enrichment graphs are shown Fig. 13.4 for both a1A pharmacophores. 

Virtual Screening Models and Focused Libraries 2D, 3D-QSAR, Pharmacophore based models Structure Based models (Docking)... 

---