Searching Screens

Fox, S., Farr-Jones, S., Sopchak, L., Boggs, A., and Comley, J., High-throughput screening searching for higher productivity, /. Biomol. Screen., 9, 354, 2004. 

We have evaluated the various approaches described above by means of simulated virtual screening searches on the MDL Drug Data Report (MDDR) database. After removal of duplicates and molecules that could not be processed using local software, a total of 102 535 molecules were available for searching. These molecules were represented by 988-bit Tripos Unity 2D fingerprints, and searched using the eleven sets of active compounds detailed in Table 1. 

Fox S. 2004. High-throughput screening searching for higher productivity. J. Biomol. Screen. 9, 354—358. 

Piericidins are the first compounds obtained by the screening search for insecticidal natural products among microbial metabolites.10 They were isolated from Streptomyces mobaraensis in 1963,11 and many piericidin derivatives have been found in microbial metabolites until now.12 Piericidins are not used as insecticides practically, but are important biological reagents because they have specific inhibitory activity toward the mitochondrial electron transport chain protein nicotinamide adenine dinucleotide (NADH)-ubiquinone reductase (complex I).13 Piericidin Ax (1 in Figure 1) is biosynthesized as a polyketide,14 but genes responsible for its biosynthesis are not yet identified. Total synthesis of piericidins A (1) was reported recently.15... 

S. Fox, S. Farr-Jones, L. Sopchak, A. Boggs, and J. Comley, High-Throughput Screening Searching for Higher Productivity, Journal of Biomolecular Screening, vol. 9, no. 4, pp. 354-358, Aug. 2004. 

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,... 

All of the search functionality described above can be accessed in CSD Version 4 via an integrated set of interactive, graphical menus. These cover the numerical, text, unit-cell and bit-screen searches but were chiefly designed to simplify the encoding... 

But the extraction of the educts and the formed products from the culture broth or buffer solution at set time intervals, and chromatographical analysis of the enzymatic reaction sometimes combined with spectrographical methods is always the burden for screenings search for the desired biocatalysts. The comparison of the metabolites with the target substance or... 

Efficient development of active substances (high-throughput screening, searching for and optimizing lead structures, clinical development)... 

Many of the false matches are eliminated by the distance search. The co-ordinate data for each structure which passes the screen search are retrieved from a disk file, the exact interatomic distances are calculated, and then compared with the set of query distances to determine whether all of the latter are present within the structure. The co-ordinate data are very bulky, and require access to backing storage for each of the molecules involved in the distance search. In addition, there is the computation associated with the calculation of the distances and their subsequent comparison with the set of query distances thus the distance search is much more time-consuming than the screen search, despite the much smaller number of structures that needs to be processed. While the distance search permits the identification of those structures which contain the precise distances in the query specification, it does not involve consideration of the overall topography of the structures, which can only be established by the final geometric search (which is discussed in detail in a later section). 

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