Mining Chemical Reactions Using Neighborhood Behavior and Condensed Graphs of Reactions Approaches

This work addresses the problem of similarity search and classification of chemical reactions using Neighborhood Behavior (NB) and Condensed Graphs of Reaction (CGR) approaches. The CGR formalism represents chemical reactions as a classical molecular graph with dynamic bonds, enabling descriptor calculations on this graph. Different types of the ISIDA fragment descriptors generated for CGRs in combination with two metrics - Tanimoto and Euclidean - were considered as chemical spaces, to serve for reaction dissimilarity scoring. The NB method has been used to select an optimal combination of descriptors which distinguish different types of chemical reactions in a database containing 8544 reactions of 9 classes. Relevance of NB - analysis has been validated in generic (multiclass) similarity search and in clustering with Self-Organizing Maps (SOM). NB compliant sets of descriptors were shown to display enhanced mapping propensities, allowing the construction of better Self-Organizing Maps and similarity searches (NB and classical similarity search criteria - AUC ROC - correlate at a level of 0.7). The analysis of the SOM clusters proved chemically meaningful CGR substructures representing specific reaction signatures.