Common substructure, definition

Similarity searching in reaction databases has gained widespread interest since it became available (in REACCS and ORAC) about two years ago. The definition of similarity of reactions in these reaction retrieval systems is based on common substructural features in the reaction centres and in the reactants. Without doubt, these definitions of reaction similarity are of great usefulness. However, we wanted to broaden the discussion of reaction similarity and search for additional helpful ideas. To achieve this we took a totally different approach to specify the similarity of reactions. Our approach is based on the idea that chemists often want to know the exact conditions for running a reaction. We assumed that similar reactions should be those that proceed under similar reaction conditions. 

Atoms and/or bonds participating in a reaction. This formal (not mechanistic) definition is based on determining the MCS (maximum common substructure) between reactant and product the parts of reactant and product outside the MCS contain the reaction centers. Reaction centers define a certain transformation of structures and group together reactions of the same... 

Another way to view similarity between 3-D structures is to focus on the pharmacophore atoms and the direction, or points, of their interaction with a target protein. The program FAMILY (142) assigns 3-D structures to families of compounds in which the variation in all distances between the points of interest are within a specified tolerance, usually 0.3-0.5 A. FAMILY uses the Bron-Kerbosh clique detection algorithm (143,144) to find these common 3-D substructures, and is rapid in execution since a typical test found that 384 compounds could be matched over seven points in under a minute on a VAX 9000. The points that are considered in the analysis are selected in an initial run of ALADDIN, and are typically the pharmacophore atoms and all heavy atoms that are attached to them. In a classification of dopaminergics, the atoms attached to these attached atoms were also used to increase the number of families found. In this example of compounds that met the pharmacophore requirements, it was shown that the set of computer-designed compounds (97) sorted itself into 36 families whereas compounds in a definitive review (145) sorted themselves into 15 families. 

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