Combining structure- and ligand-based approaches to improve site of metabolism prediction in CYP2C9 substrates.

ABSTRACT:

Purpose

Predicting atoms in a potential drug compound that are susceptible to oxidation by cytochrome P450 (CYP) enzymes is of great interest to the pharmaceutical community. We aimed to develop a computational approach combining ligand- and structure-based design principles to accurately predict sites of metabolism (SoMs) in a series of CYP2C9 substrates.

Methods

We employed the reactivity model, SMARTCyp, ensemble docking, and pseudo-receptor modeling based on quantitative structure-activity relationships (QSAR) to account for influences of both the inherent reactivity of each atom and the physical structure of the CYP2C9 binding site.

Results

We tested ligand-based prediction alone (i.e. SMARTCyp), structure-based prediction alone (i.e. AutoDock Vina docking), the

SUBMITTER: Kingsley LJ 

PROVIDER: S-EPMC4329266 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature