D Databases

Figure 5 The crystal structures for SEB and TSST-1. These structures were constructed by using data provided by Entrez s 3-D database and software for molecular modeling. Primary references for SEB and TSST-1 crystai structures are Papageorgiou etal. and Prasad ef respectiveiy.

An approach we term Virtual Screening of Virtual Libraries (VSVL) is intended to take advantage of our in-house automated synthesis capabilities. This involves the creation of large 3-D databases of virtual libraries using the Catalyst system [20]. Catalyst uses a prestored set of conformations for each molecule, so while construction of the... 

The last thing we need to do is install the Digikey database components. The setup program is located on the CD-ROM that accompanies this text. Run the program D Database setup.exe, where D is the drive letter for your CD-ROM drive. After a few moments, you will see the screen below ... 

D. Database integrity is maintained in a multi-user environment through the centralized data dictionary. 

HP- 2DPAGE Heart 2-D Database, MDC, Berlin Human heart (ventricle) http //www.mdc-berlin.de/ emu/heart/ Muller et al., 1996... 

CHEMLINE Chemical Dictionary Online National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 (301) 496-1131 Online chemical dictionary with over 500,000 records on chemical substances found in the TOXLINE, TOXBACK65, TOXBACK74, RTECS, MEDLINE, and T1>D databases, as well as the HPA TSCA Inventory. Search capability by synonyms, CAS Registry Numbers, and by classes of compounds. Prime time connect cost is S54 per hour. 

For the pharmacophore-based screening, a 3-D-pharmaco-phore feature is constmcted by structure-activity relationship analysis on a series of active componnds (26) or is dednced from the X-ray crystal stmcture of a ligand-receptor complex (27). Taking this 3-D-pharmacophore feature as a query structure, 3-D database search can be performed to select the molecnles from the available chemical databases, which contain the pharmacophore elements and may conform to the pharmacophore geometric constraints. Then the selected compounds are obtained either from commercial sonrces or from organic synthesis for the real pharmacologic assays (see Fig. 3). 

Discovery of Novel Matriptase Inhibitors through Structure-Based 3 D Database Screening... 

The pharmacophore model obtained by the mapping procedure allows 3-D database searching (Fig. 8). Database searching can identify actives in different chemotypes relative to those utilized for pharmacophore generation. This procedure is often termed as... 

ACD database and program MACCS supplied by Molecular Design Ltd. San Leandro, CA. 3-D-database programs were not available to us... 

B. Beck, A. Horn, J.E. Carpenter, and T. Clark. Enhanced 3-D databases A fully electrostatic database of AMI-optimized structures. Journal on Chemistry, Information and Computer Science, 38 1214-1217, 1998. 

Bohm, H.-J. (1998) Prediction ofbinding constants of protein ligands a fast method for the prioritization of hits obtained from dc novo design or 3 D database search programs. /. Comput. Aid. Mol. Dcs., 12, 309-323. 

Murrall NW, Davies EK. Conformational freedom in 3-D databases 1. Techniques. J Chem Inf Comput Sci 1990 30 312-316. 

The first operational system for searching a 3-D database of nontrivial size was reported in 1987 (78) since then, the field of 3-D searching has been extremely rapid growth, and there are already several documented examples of the utility of 3-D searching in real research programs, as discussed in Section IV. This progress has occurred because of the converging interests... 

Perret, D., Database on Capillary Electrophoresis, with entries to December 1995. 

K. D. Stewart, S. Loren, L. Frey, E. Otis, V. Klinghofer, and K. I. Hulkoweii Bioorg. Med. Chem. Lett., 8, 529 (1998). Discovery of a New Cyclooxygenase-2 Lead Compound Through 3-D Database Searching and Combinatorial Chemistry. 

H.-J. Bohm,/. Comput.-Aided Mol. Des., 12,309 (1998). Prediction of Binding Constants of Protein Ligands A Fast Method for the Prioritization of Hits Obtained from De Novo Design or 3-D Database Search Programs. 

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