Cart
Letter
SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism
Full Text HTML
Hi-Res PDFPurchase the full-text
- PDF/HTML,
figures/images,
references and tables,
(where available)
Funding Statement
We thank the Benzon Foundation (support of P.R. and D.E.G.), the Danish medical research council (support of L.O.), NIH Grant 1P20HG003899-01 (RECCR) (support of C.B. and J.Z.), and the RPI Center for Biotechnology and Interdisciplinary Studies (support of C.B. and J.Z.).
Section:Abstract
SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. This is a major advantage, because it makes SMARTCyp very fast. Other advantages are that experimental data are not a prerequisite to create the model, and it can easily be integrated with other methods to create models for other cytochrome P450 isoforms. Benchmarking tests on a database of 394 3A4 substrates show that SMARTCyp successfully identifies at least one metabolic site in the top two ranked positions 76% of the time. SMARTCyp is available for download at http://www.farma.ku.dk/p450.
Keywords (keywords):
Cytochromes P450; metabolism; DFT; density functional theory; hemeCiting Articles
Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 5 ACS Journal articles (5 most recent appear below).
Computational Prediction of Metabolism: Sites, Products, SAR, P450 Enzyme Dynamics, and Mechanisms
Johannes Kirchmair, Mark J. Williamson, Jonathan D. Tyzack, Lu Tan, Peter J. Bond, Andreas Bender, and Robert C. GlenJournal of Chemical Information and Modeling2012 Article ASAPComputational Prediction of Metabolism: Sites, Products, SAR, P450 Enzyme Dynamics, and Mechanisms
Johannes Kirchmair, Mark J. Williamson, Jonathan D. Tyzack, Lu Tan, Peter J. Bond, Andreas Bender, and Robert C. GlenJournal of Chemical Information and Modeling2012 Article ASAPMetabolism of xenobiotics remains a central challenge for the discovery and development of drugs, cosmetics, nutritional supplements, and agrochemicals. Metabolic transformations are frequently related to the incidence of toxic effects that may result ...
Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6
Patrik Rydberg and Lars OlsenACS Medicinal Chemistry Letters2012 3 (1), 69-73Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6
Patrik Rydberg and Lars OlsenACS Medicinal Chemistry Letters2012 3 (1), 69-73A ligand-based method based on the SMARTCyp approach that predicts the sites of cytochrome P450 2D6-mediated metabolism of druglike molecules has been developed. The method uses only two descriptors besides the reactivity from SMARTCyp: the distance to a ...
IDSite: An Accurate Approach to Predict P450-Mediated Drug Metabolism
Jianing Li, Severin T. Schneebeli, Joseph Bylund, Ramy Farid, and Richard A. FriesnerJournal of Chemical Theory and Computation2011 7 (11), 3829-3845IDSite: An Accurate Approach to Predict P450-Mediated Drug Metabolism
Jianing Li, Severin T. Schneebeli, Joseph Bylund, Ramy Farid, and Richard A. FriesnerJournal of Chemical Theory and Computation2011 7 (11), 3829-3845Accurate prediction of drug metabolism is crucial for drug design. Since a large majority of drugs’ metabolism involves P450 enzymes, we herein describe a computational approach, IDSite, to predict P450-mediated drug metabolism. To model induced-fit ...
Structure-Based Site of Metabolism Prediction for Cytochrome P450 2D6
Samuel L. C. Moors, Ann M. Vos, Maxwell D. Cummings, Herman Van Vlijmen, and Arnout CeulemansJournal of Medicinal Chemistry2011 54 (17), 6098-6105Structure-Based Site of Metabolism Prediction for Cytochrome P450 2D6
Samuel L. C. Moors, Ann M. Vos, Maxwell D. Cummings, Herman Van Vlijmen, and Arnout CeulemansJournal of Medicinal Chemistry2011 54 (17), 6098-6105Realistic representation of protein flexibility in biomolecular simulations remains an unsolved fundamental problem and is an active area of research. The high flexibility of the cytochrome P450 2D6 (CYP2D6) active site represents a challenge for accurate ...
RS-Predictor: A New Tool for Predicting Sites of Cytochrome P450-Mediated Metabolism Applied to CYP 3A4
Jed Zaretzki, Charles Bergeron, Patrik Rydberg, Tao-wei Huang, Kristin P. Bennett, and Curt M. BrenemanJournal of Chemical Information and Modeling2011 51 (7), 1667-1689RS-Predictor: A New Tool for Predicting Sites of Cytochrome P450-Mediated Metabolism Applied to CYP 3A4
Jed Zaretzki, Charles Bergeron, Patrik Rydberg, Tao-wei Huang, Kristin P. Bennett, and Curt M. BrenemanJournal of Chemical Information and Modeling2011 51 (7), 1667-1689This article describes RegioSelectivity-Predictor (RS-Predictor), a new in silico method for generating predictive models of P450-mediated metabolism for drug-like compounds. Within this method, potential sites of metabolism (SOMs) are represented as “...
Tools
-
Add to Favorites
-
Download Citation
-
Email a Colleague -
Permalink
Order Reprints
Rights & Permissions
Citation Alerts
History
- Published In Issue June 10, 2010
- Article ASAPMarch 15, 2010
- Received: January 21, 2010
Accepted: March 04, 2010
ACS
Network
Facebook
Tweet This
CiteULike
Newsvine
Digg This
Delicious
