Three-dimensional molecular database pharmacophore searching

THREE-DIMENSIONAL MOLECULAR DATABASES AND PHARMACOPHORE SEARCHING... 

Varady J, Wu X, Fang X, Min J, Hu Z, Levant B, Wang S. Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor discovery of novel and potent D3 ligands through a hybrid pharmacophore-and structure-based database searching approach. / Med Chem 2003 46 4377-92. 

The database search process starts with a rapid screening process within which molecules possessing properties required from potential hits are sorted out from those that can be excluded a priori. The screen involves substructure match followed by screens matching three-dimensional pharmacophore features, molecular shapes or exclusion volumes and text constraints (ID properties) if present in the query (through Oracle). All this greatly reduces the number of potential hit compounds in the database. The next step of the search pro-... 

Three-dimensional database searching is a powerful new tool for developing novel synthetic targets. This technique can be used in cases where an enzyme/receptor 3-D structure is known, or alternatively in the case where the enzyme/receptor structure is unknown. In the latter case an active compound or series of compounds can be used to develop a pharmacophore model. Because 3-D database searching requires biological data stored in 2-D databases and molecular modelling techniques, we expect to see increased integration of 2-D and 3-D database/ information systems. 

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