Similarity Searching Structures System

MassLib is not only applicable to spectrum similarity searches. The system contains an MS-specific coding technique for chemical structures based on 160 structure descriptors. This enables the spectroscopist to apply chemometric techniques to analyse the results of spectral similarity searches in the structure space. 

CACTVS is a chemical information system which provides 2D and 3D complete structure, substructure, and similarity search on plain files of structures. The... 

To seat ch for available starting materials, similarity searches, substructure searches, and some classical retrieval methods such as full structure searches, name searches, empirical formula searches, etc., have been integrated into the system. All searches can be applied to a number of catalogs of available fine chemicals (c.g, Fluka 154]. In addition, compound libraries such as in-housc catalogs can easily be integrated. 

Current chemical information systems offer three principal types of search facility. Structure search involves the search of a file of compounds for the presence or absence of a specified query compound, for example, to retrieve physicochemical data associated with a particular substance. Substructure search involves the search of a file of compounds for all molecules containing some specified query substructure of interest. Finally, similarity search involves the search of a file of compounds for those molecules that are most similar to an input query molecule, using some quantitative definition of structural similarity. 

Data storage and querying are the most fundamental requirements of all informatics systems. Thanks to the Oracle Extensibility Framework (a.k.a. Oracle Data Cartridge Technology), chemical structure data can be stored and queried using direct SQL and special query operators, such as substructure search, flexmatch search, similarity search, and formula search. Also, some indexing techniques make these otherwise slow searches fast. Detailed discussions about these databases and cartridges are beyond the scope of this book. Please refer to the vendor s website and product documentation for more information. 

PubChem is organized as three linked databases within the NC8I s Entrez information retrieval system. These are PubChem Substance. PubChem Compound, and PubChem BioAssay. Pubchem also provides a fast chemical structure similarity search tool. More information about using each component database may be found using the links above. 

This chapter focuses on step 3. For step 1, descriptors may include property values, biological properties, topological indexes, and structural fragments. The performance of these descriptors and forms of representation have been analyzed by Brown and Brown and Martin. Similarity searching for step 2 has been discussed by Downs and Willett characteristics of various similarity measures have been discussed by Barnard, Downs, and Willett. " For step 4, little has been published specifically about visualization and analysis of results for chemical data sets. Flowever, most publications that focus on implementing systems that utilize clustering do provide details of how the results were displayed or analyzed. 

Table 2.2 also lists three publicly available databases commonly used in drug research. PubChem is accessed through the National Library of Medicine (Austin et al., 2004) and contains chemical structure information and corresponding activity across a number of biological assays. The system links the compound information with biomedical literature and it is possible to perform web-based similarity searching. PubChem also enables one to download files with structures to perform chemoinformatic analysis off-line. 

The biggest exception to this, of course, is the GABA system which is associated with a variety of active drugs. Besides the older picrotoxinin (I) and bicuculline (II), there are barbiturates (III), nipecotic acid (IV), muscimol (V), benzodiazepines (VI), baclofen (VIII), and avermectins to guide the search for active leads. The recent suggestion of similarities in structure and mode of action of lindane, cyclodienes and picrotoxinin analogs (J ) throws open even more possibilities. 

The last few years have seen substantial interest in the development of similarity searching systems (47, 48) in which the compounds in a database are ranked in order of decreasing similarity with an input query structure (rather than identifying those compounds that contain the query as in substructure searching). To implement similarity searching, one must provide an appropriate measure of intermolecular structural similarity, and many such measures are available (49). 

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