This paper describes methods for modelling two enzyme families, flavin-containing monoxygenases (FMOs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), to predict reactivity to drug metabolism. It builds on the metabolism modelling methods within the StarDrop™ P450 module.
There are several enzyme families involved throughout the drug metabolism process. These include flavin-containing monooxygenases (FMOs), which can catalyse oxidation reactions during the modification phase of drug metabolism, and uridine 5′-diphospho-glucuronosyltransferases (UGTs), the most important class of drug conjugation enzymes. UGTs catalyse glucuronidation reactions.
In this work, the team shares a study of the rate limiting steps of product formation for FMOs and UGTs, based on density functional theory calculations. They build models to calculate the activation energy of the rate-limiting steps for FMO oxidation and UGT glucuronidation at potential sites of metabolism on a compound, validated with experimental data.
M. Öeren, P. J. Walton, P. A. Hunt, D. J. Ponting, M. D. Segall, J. Comput.-Aided Mol. Des., 2021, 35(4) pp. 541-555
Find out more
Visit the journal webpage to read the final published version of this article, or take a look at our related webinar on modelling FMOs and UGTs, featuring two of the authors of this paper, Mario and Matt, discussing the work in more detail.
Want more information on our latest metabolism prediction developments? Some of our latest resources are listed below:
Peer-reviewed article: Predicting Regioselectivity of Cytosolic SULT Metabolism for Drugs
- Webinar: Integrated prediction of phase I and II metabolism
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