Similarity Searching in Databases of 3D Structures

It will be clear from the material presented earlier that 2D similarity searching (either in its basic form or in its subsimilarity or supersimilarity forms) has become a standard retrieval option in chemical information systems 

We have noted previously that similarity measures can be either local or global in character, depending upon whether they involve the generation of an alignment of the target structure with a database struaure, and we shall use this characteristic to provide an initial subdivision of the 3D similarity measures that have been reported to date in the literature. The next section also considers the extension of these measures to encompass flexible 3D molecules and the subject of docking, which is probably the most important application, thus far, of 3D similarity measures in the design of novel bioactive compounds. 

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In the earlier section on the Chemical Abstracts Service (CAS), we gave a brief overview of the range of similarity measures that are under investigation by Fisanick et al. and described the novel descriptors that these workers have developed for similarity searching in databases of 2D structures. Their studies have also involved both geometric and property based 3D similarity measures in all, a molecule is characterized by a maximum of no fewer than 3172 different features. 

Schuffenhauer A, Gillet VJ, Willett P. Similarity searching in files of 3D chemical structures analysis of the BIOSTER database using 2D fingerprints and molecular field descriptors. J Chem Inf Comput Sci 2000 40 295-307. 

Raymond, J.W. and Willett, P. Similarity searching in databases of flexible 3D structures using smoothed bounded distance matrices. /. Chem. Inf. Comput. Sci. 2003, 43, 908-916. 

We now describe an important application of 3D similarity searching, one that is rather different in concept from those discussed thus fer. Specifically, we discuss the use of similarity-based techniques to identify molecules in a database of 3D structures that are complementary to a biological receptor site... 

Many different structural descriptors have been developed for similarity searching in chemical databases [4] including 2D fragment based descriptors, 3D descriptors, and descriptors that are based on the physical properties of molecules. More recently, attention has focused on diversity studies and many of the descriptors applied in similarity searching are now being applied in diversity studies. Structural descriptors are basically numerical representations of structures that allow pairwise (dis)similarities between structures to be measured through the use of similarity coefficients. Many diversity metrics have been devised that are based on calculating structural (dis)similarities, some of these are described below. 

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