Generics database, searching

Figure 5.11. Generic approaches to identify interacting proteins within complexes. The complex is isolated from cells by affinity purification using a tag sequence attached to a protein known to be in the complex. Alternatively, the complex can be immunprecipitated with an antibody to one of the proteins in the complex. The proteins are resolved by polyacrylamide gel electrophoresis, proteolyzed, and the mass of the resulting peptides is determined by mass spectrometry. Alternatively, the proteins can be proteolyzed and the resulting peptides resolved by liquid chromatography. The peptide masses are then determined by mass spectrometry and used for database searching to identify the component proteins.

The CDD staff concluded that MACCS could not rephcate the registration process of CSIS. It also did not provide the sophisticated generic substructure searching capabilities which are used in a least 45% of the searches executed by the CDD staff. The absence of an interface with the department s ancillary databases was another serious deficiency of MACCS. 

In chemical structure terms, he may wish to search for an exact structure of a reactant or product (although this is probably more useful with an in-house than with a literature database) or for a substructure in a reactant or product. However, what he would most like to do is generic reaction search. 

Gillet, V.J., Downs, G.M., Holhday, J.D., Lynch, M.F., Dethlefsen, W. Searching a Full Generics Database . In these Proceedings. 

Figure 7. Results of searching 60 generic queries against the full generics database...

A structure search of chemical substances can be performed in the chemical structure databases. The structure query can be input using a graphical structure editor. The following search methods are possible, depending on the type of structure database. The structure search capabilities depend on the software system. Here, the focus is on the implementation of STN International exact structure search, family search, substructure search, similarity search, generic (Markush) search, and reaction search. 

Markush searches are generic substructure searches. It should be clear that both structure queries and structure files may contain specific and/or generic Structures. In a Markush search generic chemical structures are searched against a database which contains specific or generic structures. The first type of database is a registry file, e.g., the CAS REGISTRY, and the second type is a Markush file, e.g., MaRPAT (see Structure Representation). 

MPHARM is a companion database to the bibHographic PHARM. It contains the specific and generic stmcture records for compounds disclosed ia pateats iacluded ia the bibHographic database. Compouad aumbers located ia MPHARM can be searched ia PHARM to retrieve the corresponding bibHographic records (100). 

We should not minimize the effects that electronic searching of patents has had on the business of research. In 1990, CAS introduced MARPAT, which is a database of Markush (generic) structures found in patent documents [1]. This database provided a valuable tool for patent searching in a more comprehensive way than had been available previously. In 1995, CAS launched SciFinder, which provided access to the patent literature for chemists on their desktops. Using the SciFinder interface, one may search for research topics, authors, companies, or structures/reactions. From a practical viewpoint, SciFinder did more to enhance the searching capabilities of the medicinal chemist than any other tool. Even today, SciFinder continues to provide a first pass through the patent literature when chemists want to include patents in their searching. Indeed, when a search is performed, patent references are included in the answer set. Only very recently have there been additional tools to search the patent literature that have found widespread use. 

Each series has a set of keywords that specify the series properties. The database can be searched by author name, citation, compound name, SMILES or keywords. A search of a substructure or a generic pattern is also possible. The pattern of molecules in a series is highlighted. Compounds in most series include the same or parent structures with different functional groups. Many series also include existing drugs or other lead compounds. A possible correlation can be derived between the structure and the measured bioactivity. 

WPIM (World Patents Index Markush), produced by Derwent Publications, Ltd., contains the specific and generic structure records for compounds in the patents included in Derwent Sections B (Farmdoc), C (Agdoc), and E (Chemdoc) since 1987. Sources include patents from 29 industrialized countries as well as European and PCT patents and also items from Research Disclosure and International Technology Disclosures. The compound numbers of relevant references found in WPIM can be searched in Derwent s WPI database to retrieve the corresponding bibliographic information. 

Another searching capability is required by the need to find a partial structure or substructure in a database that includes generic structures. The ability to do a substructure search is standard in modem chemical structure information systems. The problem is more complicated when generic structures must be searched, yet even more necessary since the generic might represent millions of specific structures. The query in Fig. 8 is compared with the generic structure to find the set of specific structures. 

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