Automated analysis of enzyme reaction mechanisms

Enzymes can be classified by the kind of chemical reactions they catalyze (e.g. The International Union of Biochemistry and Molecular Biology (IUBMB) enzyme classification). We present a novel method called “EC-BLAST” to search and compare enzymes based on chemical reactions.
This robust and efficient tool is based on an in-house algorithm. It computes atom-atom mapping between the reactant(s) and product(s) of a reaction and marks bond changes. A user can search similar enzymes based on the reactions’ substrate specificity, reaction centers and bond changes, or even a combination of these queries. The results are ranked based on a scoring function, highlighting the degree of conserved/variable regions between reactions. This information complements knowledge obtained from protein sequence/structure based studies. The knowledge of annotated reaction centers from the processed reactions can be used to predict the enzymes that can potentially transform or act on a query metabolite(s).

This tool will find application in various life science fields, and can be used to find alternate/missing enzymes in metabolic pathways, in drug discovery and toxicity based studies that not only require alternate pathways but also seek enzyme re-engineering. Additionally, it will help shed light on the evolutionary aspects of enzyme mechanisms. It can potentially provide a basic framework for both academic and industrial research and may eventually lead to a new classification system for enzymes.

No relevant conflicts of interest declared.