Chemistry Reference
In-Depth Information
Based on the GRID descriptors for cytochrome P450 enzymes and substrate
potential [5], metabolism can be assessed at all possible sites of the molecular
structure by assigning each atom a probability of metabolism [30]. The accuracy
of the program exceeds more than 85%, providing the metabolites structure
obtained in a ranking derived from the site of metabolism predictions. The method
highlights the atoms in the molecule that contribute to the prediction, directing the
molecule in the cytochrome cavity. Modifying the contributing regions that
influence mostly the site of metabolism can avoid inhibitory issues such as the
direct blocking of the primary site of metabolism, which could create a
cytochrome inhibitor.
Figure 1:
Metasite metabolism prediction (http://www.moldiscovery.com/soft_metasite.php).
As part of an earlier project begun in 1985 by CompuDrug, MetabolExpert was
developed with the goal of creating a model for the prediction of chemical
transformations in living systems or in a controlled environment, using an expert
