Searching structural fragments

The search for structural fragments (substructures) is very important in medicinal chemistry, QSAR, spectroscopy, and many other fields in the process of perception of pharmacophore, chromophore, or other -phores. 

In order to enhance our ligand-based query hypothesis, the structural fragments of the initial query were generalized but linked with the same distance constraints. A search of this final query (see Fig. 4-10) in the same list yielded 690 hits and a statistically significant correlation of the presence of this enantiophore and the enan-tioselectivity of the compounds was found (94 % of those are well resolved on Chi-ralcel OD). Note that out of the 4203 compounds of the Chiralcel OD domain search, a 2D search found 1900 structures that contain the substructural features of the generalized query. 

Structural queries and graphs. A simple but very popular form of similarity searching is the detection of structural fragments or substructures that are shared by query and database compounds. Figure 1.10 illustrates the idea of substructure searching. 

TerraBase Inc. (www.terrabase-inc.com) is a Canadian company specializing in databases for QSAR-type research. It provides the data in a normalized, logarithmic fashion for direct use in QSAR development. It has several CD-ROM products specialized to the endpoint of interest and the application of chemicals. These databases can be searched by a variety of means, including chemical structure fragments. Information includes use, physicochemical properties, and over 100 types of toxicity data to aquatic and terrestrial species. A complete list of the types of data covered is available on the company s website. 

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. 

Sayle has noticed that direct assignment of typical pK values according to detected ionizable atom types predicts pK values for simple molecules with standard deviation of 0.95 log units. The observation that similar molecules, or similar molecular fragments, have similar pK is the basis of the last class of methods. A database containing either complete structures or structural fragments and experimental pK values is searched for the nearest neighbors of the compound in question. Correction factors may be eventually applied to the observed pK values. Of course, treatment of microspeciation is not possible in this approach. Software in this group... 

The substructure list representation can be considered as a one-dimensional representation of a molecule and consists of a list of structured fragments of a molecule the list can only be a partial list of fragments, functional groups, or substituents of interest present in the molecule, thus not requiring a complete knowledge of the molecule structure. The descriptors derived by this representation can be called ID-descriptors and are typically used in - substructural analysis and -> substructure searching. 

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