2D substructure searching

Computer Representations of Molecules, Chemical Databases and 2D Substructure Searching... 

Figure 8.2 Example of a 2D substructure search. The search is for the diphenyl ether query substructure at the top of the figure, below which are shown five of the hits resulting from a search of the National Cancer Institute database of molecules that have been tested in the US government anticancer program (see URL http //dtp.nci. nih.gov/). This database is also used for the search outputs shown in Figures 8.3 and 8.4.

Historically, ligand structure-based design has been the most widely used approach to the design of target-directed chemical libraries. Methods that start from hits or leads are among the most diverse, ranging from 2D substructure search and similarity-based techniques to analysis of 3D pharmacophores and molecular interaction fields (Fig. 15.2). 

Figure 9.13. Example 2D substructure search queries with various atom and bond query features. The more features that are present, the more flexible the search becomes, but the search may also require more time to complete. There is a trade-off between putting the flexibility into the database (i.e., storing and indexing multiple forms of a structure) and putting the flexibility into the search query and the search software.

Table 3.1. Alphanumeric instruction set for 2D substructure search definition within CSD System Versions 3 and 4...

Secondly, there is very little control over the size of the output that is produced by a particular query substructure. Without a detailed knowledge of the contents of the file, the searcher will be unable to predict a priori how many database structures will satisfy the structural constraints defined by a given query. Even in the case of a 2D substructure search of an in-house file, the specification of a common ring system or of several possible substituents at a particular location (or locations) can result in the retrieval of several thousands of structures (unless it is also possible to specify other constraints such as... 

Fuzzy 2D substructure searching is an extension of substructure searching to the minor extent that it permits the expansion of the query formulation vocabulary to include topological features and substructural wildcards described above. This involves the retrieval of all entities in a CIR system that contain the user-defined partial structure and that satisfy whatever wildcard specification pattern has been specified. The query identifies the partial structure and simple wildcard substitution patterns exactly. As with substructure searching, the use of query features on a partial structure will always identify structures which are equal in size or larger than the query. 

---