Background: Contamination of the environment with bioactive chemicals
has emerged as a potential public health risk. These substances that may cause
distress or disease in humans can be found in air, water and food supplies. An open
question is whether these chemicals transform into potentially more active or toxic
derivatives via xenobio... read moretic metabolizing enzymes expressed in the body. We present a
new prediction tool, which we call PROXIMAL (Prediction of Xenobiotic Metabolism) for
identifying possible transformation products of xenobiotic chemicals in the liver.
Using reaction data from DrugBank and KEGG, PROXIMAL builds look-up tables that
catalog the sites and types of structural modifications performed by Phase I and
Phase II enzymes. Given a compound of interest, PROXIMAL searches for substructures
that match the sites cataloged in the look-up tables, applies the corresponding
modifications to generate a panel of possible transformation products, and ranks the
products based on the activity and abundance of the enzymes
Keywords: Xenobiotic metabolism, Environmental chemical, Molecular
substructure, Phase I and Phase II enzymes.