Screen Searching Substructures

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-... 

Baldi, Benz et al, 2007]. In effect, in folded vectors, different fragments can set the same bit causing fragment collisions. In any case, this does not affect the effectiveness of screening because false positives can be returned for an atom-by-atom matching, but compounds with the searched substructure vdll never be rejected. 

Other common descriptors derived from substructure-based methods are discussed below. Among these, hash structural codes, structural keys, and fingerprints are mostly applied in virtual screening and substructure searching, whereas pharmacophore-based descriptors are more successful in similarity/diversity analysis and QSAR/QSPR studies. 

Cringean, J.K and Lynch, M.F. (1989) Subgraphs of reduced chemical graphs as screen for substructure searching of spedfic chemical structures./. Inform. Sci., 15, 211—222. 

Cringean JK, Lynch MF. Subgraphs of reduced chemical graphs as screens for substructure searching of specific chemical structures. J Inf Sci 1989 15 211-222. 

The two main applications of molecular descriptors have been for screens in substructure searching [4] and for attributes in similarity calculations [5]. Historically, many descriptors were developed first for substructure searching (see Chapter 19 of this book) and then used in similarity calculations for applications such as similarity analysis, clustering, combinatorial library design, and data mining (see Chapters 14,... 

The development of efficient and effective substructure search systems has been based on a fast screening search to eliminate compounds that cannot match the query,... 

Since the earliest MGS work was impracticable, we began instead to look at a more readily attained and more practically useful objective indexing of chemical structures in order to provide screens for substructure search. Note, however, that the stimulus came from an analogous linguistic problem context - a topic to which I will return again. 

An extension of SOCRATES to handle chemical reactions, called CONTRAST, has also been developed at Sandwich, again with some collaboration from Peter Willett at Sheffield. In SOCRATES the precursors of our company compounds are stored in the compound registry file, and so application of a reaction site detection algorithm to the starting material and product generates a set of modified connection tables and fragment screens, and a set ofreaction bit-screens. The substructure search graphical structure input menu was modified to enable the chemist to identify the atoms involved in the reaction, but otherwise is essentially the same interface as in SOCRATES. 

Screens traditionally denote the presence or absence of predefined atom-, bond-, or ring-centered substructural fragments. However, one may also use subgraphs of the molecules to generate a set of molecular fingerprints to use as the screen. The screen search checks each structure for those screens present in the query substructure. For maximum effeaiveness the fragments included should occur independently and with equal frequency in the database. " ... 

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