Prioritizing Compounds, Step 4: Predicting Sites of Cytochrome P450 Metabolism
Predicting Sites of Cytochrome P450 Metabolism
The URL of our drug candidate will be used to submit this compound to two models predicting cytochrome P450 sites of metabolism, namely
- SmartCYP (http://pirin.uni plovdiv.bg:8080/malaria/model/10, Rydberg P. et al., SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism, ACS Medicinal Chemistry Letters 2010, 1(3), 96-100) and
- SOME (http://pirin.uni plovdiv.bg:8080/malaria/model/21, Zheng M. et al., Site of metabolism prediction for six biotransformations mediated by cytochromes P450, Bioinformatics 2010, 25(10): 1251-1258)
Model prediction is done analogously to the two models used in this exercise. Go to http://pirin.uni plovdiv.bg:8080/malaria/model/10 and copy the compound URL into the text box.
When completed, the results will be available at
http://pirin.uni plovdiv.bg:8080/malaria/compound/458166/conformer/773441?feature_uris[]=http%3A%2F%2Fpirin.uni plovdiv.bg%3A8080%2Fmalaria%2Fmodel%2F10%2Fpredicted
and will consist of information on which atoms are of rank 1, 2, 3 or lower. Higher rank means a more labile site. This information will be best viewed graphically, which could be achieved by the following URL
http://pirin.uni plovdiv.bg:8080/malaria/compound/458166/conformer/773441?model_uri=http://pirin.uni plovdiv.bg:8080/malaria/model/10 (see the following Figure).
The colour code for the result can be found by clicking on the “legend” link on the model page.
Similarly, the SOME model predictions are visualized via
http://pirin.uni plovdiv.bg:8080/malaria/compound/458166/conformer/773441?model_uri=http://pirin.uni plovdiv.bg:8080/malaria/model/21
And the color code is
The color-coding of the metabolic sites according to the type of metabolic reaction taking place allows the user – with a little knowledge in organic chemistry – to work out the metabolites of the compound.
To obtain the predictions of the sites of metabolism for the entire dataset, one can use the following URL: http://pirin.uni plovdiv.bg:8080/malaria/compound?type=smiles&property=&search=Low+%28Class+I%29&feature_uris[]=http://pirin.uni plovdiv.bg:8080/malaria/feature/190&feature_uris[]=http://pirin.uni plovdiv.bg:8080/malaria/feature/179&feature_uris[]=http://pirin.uni plovdiv.bg:8080/malaria/feature/258&feature_uris[]=http://pirin.uni plovdiv.bg:8080/malaria/feature/259&model_uri=http://pirin.uni plovdiv.bg:8080/malaria/model/21&w=250&h=250