Queries

Table 1 Breakdown of major queries through NDTnet sorted by groups...

The ROSDAL (Representation of Organic Structures Description Arranged Linearly) syntax was developed by S. Welford, J. Barnard, and M.F. Lynch in 1985 for the Beilstein Institute. This line notation was intended to transmit structural information between the user and the Beilstein DIALOG system (Beilstein-Ohlme) during database retrieval queries and structure displays. This exchange of structure information by the ROSDAL ASCII character string is very fast. 

Besides specifications on atoms, bonds, branches, and ring closure, SLN additionally provides information on attributes of atoms and bonds, such as charge or stereochemistry. These are also indicated in square [ ] or angle < > brackets behind the entity e.g., trans-butane CH3CH=[s=t]CHCH3). Furthermore, macro atoms allow the shorthand specification of groups of atoms such as amino adds, e.g., Ala, Protein2, etc. A detailed description of these specifications and also specifications for 2D substructure queries or combinatorial libraries can be found in the literature [26]. 

The JME can also serve as a query input tool for structure databases by allowing creation of complex substructure queries (Figure 2-130), which are automatically translated into SMARTS [22]. With the help of simple HTML-format elements the creation of 3D structure queries is also possible, as were used in the 3D pharmacophore searches in the NCI database system [129]. Creation of reac-... 

Figure 3-5. The search for a) oxidations of primary alcohols to carboxylic acids will obtain reaction b) as a hit, although this reaction is in reality a hydrolysis of an ester, c) The correct specification of the query to obtain reactions invoivingthe oxidation of aicohols to carboxyiic acids.

Specification of the reaction center is important for many queries to reaction databases. 

Among many approaches to manipulating a relational database, the most prevalent one is a language called SQL (Structured Query Language) [2]. 

Research project databases include information on abstracts and reports categorized by research projects. Such factual databases allow one to search for projects in various fields of science and technology wdth numeric and textual queries. 

Thus, if the user wants to look for literature including requested chemicals or reactions, it is possible to query the database by the first option Chemical Substance or Reaction , The compound can be entered as a query in three different ways drawing the chemical structure in a molecule editor (Chemical Structure) searching by names or identification number, such as the CAS Number (Structure Identifier) and searching by molecular formula (Figure 5-12). 

Once the query has been entered, the search for the compound can be executed with an exact match or a substructure search. All resulting matches, up to 10 000,... 

If the query provides thousands of hits, the analyze features are particularly advantageous. One method is to analyze the results by any of the criteria that arc listed, c.g., by language (default), author names, journals, puhlication year, and so on. If one specification is selected and the choice is modified, the hit list will be updated. A more specific analysis is available with the Refine" option. where the user has the opportunity to choose one of eight criteria (including the search topics above) with further individual input. Several refinements of the hit list can reduce the result to a concise list of literature. To read the abstract of an article, the microscope button (to the right of the citation) has to be pressed (Figure 5-15). 

The reinaining five search topics (Research Topic, Author Name, Document Identifier, Company Namc/Organii ation, and Browse Table of Contents arc conducted in a similar fashion, with the input being the only difference between the criteria. Thus, in Research Topic" the entry can be any, or even several, keywords or phrases. In "Author Name", literature written by a specific author will be Found, including alternative spelling, Document Identifier" can also be entered directly in the query. Document identifiers arc CA abstract numbers, patent numbers, patent application numbers, or priority application numbers. The last two search topics (Company Name/Organi2ation, and Browse Table ofContents) allow one to search for literature from specific companies or to view the list of journals which are available in the database. 

In every step of the query, users can sec examples given by the program, in order to guide them through the literature search. Thus, a novice user can operate this system immediately. 

It Is cmphasi < cd that both versions of the generic structure query may include the parent compound and monochlorinated derivatives. 

The protein sequence database is also a text-numeric database with bibliographic links. It is the largest public domain protein sequence database. The current PIR-PSD release 75.04 (March, 2003) contains more than 280 000 entries of partial or complete protein sequences with information on functionalities of the protein, taxonomy (description of the biological source of the protein), sequence properties, experimental analyses, and bibliographic references. Queries can be started as a text-based search or a sequence similarity search. PIR-PSD contains annotated protein sequences with a superfamily/family classification. 

The Web-based graphical user interface permits a choice from numerous criteria and the performance of rapid searches. This service, based on the chemistry information toolkit CACTVS, provides complex Boolean searches. Flexible substructure searches have also been implemented. Users can conduct 3D pharmacophore queries in up to 25 conformations pre-calculated for each compound. Numerous output formats as well as 2D and 3D visuaHzation options are supplied. It is possible to export search results in various forms and with choices for data contents in the exported files, for structure sets ranging in size from a single compound to the entire database. Additional information and down-loadable files (in various formats) can be obtained from this service. 

Figure 5-24. Query drawn for guidir g examples for the reduction of 3 -methylcyclohex-2-enoiie to 3-inethylcyclohex-2-enol.

First, a quei y must be drawn using the MOL" ISIS/Draw program. By using this reaction query, a eurrent reaction search " can be performed. This type of reaction retrieval compares the starting material and the product of the reaction query with all the reactions in the CIRX database. Both query structures must match exactly, including the implicit hydrogen atoms not shown in the reaction query. In this case, one hit is found in the CIRX databases. 

The next abstraction level of reaction retrieval is a so-called reaction substructure search in which both query structures arc considered as substructures. In the case of a reaction substructure search, no hydrogen atoms arc added internally during the execution of the search. Atoms which have their valencies not completely saturated are considered as open sites, where any hind ofelement could be bonded. 

With this query 1 16 hits were found in the CIRX databases. The first hit of this hit list is shown in Figure 5-25. 

Figure 5-26. Reaction query with atom-atom mapping numbers.

Figure 5-28. Reaction query for Example 2 "R indicates that the bond must be part of a ring system, and "53 represents an atom with three non-hydrogen attachments. The Chiral" flag is necessary to retrieve only molecules with the identical absolute stereoconfiguration.

In the worst case, the backtracking algorithm will form a search tree of depth n, where n is the number of atoms in the query graph. Also, in this case a separate sub-tree search process for each atom of the target graph will be initiated. That is why the linear multiplier m is apphed to Eq. (7). 

Asymmetric simhaiity measures allow fuzzy super- and substructure searching. A substructure search is defined as looking for structures containing the given query and a superstructure search is defined as looking for structures embedded in the given query. In both cases asymmetric local similarity is estimated. 

---