About SMARTaox

History of SMARTaox

The work that has lead to the development of SMARTaox started in 2014 when Marco Montefiori joined the group as PhD student. Marco Montefiori's PhD study was part of the ARIADME project, an Initial Training Network (ITN) project financed by EU. Later Khanhvi Phuc Tran joined the project as part of her Master project. Marco showed for a series of aldehyde oxidase (AO) substrates, that the electrostatic potential (ESP) partial charges were good markers for prediction of the site-of-metabolism (SOM) for AO substrates [1].

In 2017 the first version of the SMARTaox program was developed based on the same principle as the SMARTCyp program for prediction of CYP mediated SOM. Late 2017 the first web-server for prediction of SOM of AO substrates was launced.

The SMARTaox program is based on data from DFT calculations on a set of relatively simple model compounds. For each fragment the ESP charges were determined. Thus, the SMARTaox program contains a library of precalculated ESP charges for the most common fragments present in known drug compounds. By SMARTS matching the most similar fragment in the molecule to be predicted is identified and the ESP charges assigned to the relevant atoms in the molecule. The SMARTaox program uses similar corrections for the accessibility of the various atoms (solvent accessible surface area by the 2DSASA algorithm, RelativeSpan and Span2End) as the SMARTCyp program. The effect of these correction on the predictions has not yet been studied in details.

Current version of SMARTaox

The SMARTaox program is a Python 3 program based on the Django framework and using the ChemLib, Flask and RDKit libraries. The current version of SMARTaox may not yet handle all possible AO substrates. The current version of SMARTaox works on Safari and Crome. Frefox and Internet Explorer have not tested yet. Please, send comments, suggestions for improvements etc. to Flemming Steen Jørgensen (E-mail: fsj@sund.ku.dk)

Developers

SMARTaox has been developed by Marco Montefiori, Khanhvi Phuc Tran, Flemming Steen Jørgensen, and Lars Olsen.

Marco Montefiori

E-mail: marco.montefiori.87@gmail.com
Work done at: University of Copenhagen
Present address: CNR-ICRM, Milan, Italy

Khanhvi Phuc Tran

E-mail: nzr548@alumni.ku.dk
Work done at: University of Copenhagen

Flemming Steen Jørgensen

E-mail: fsj@sund.ku.dk
ORCID: orcid.org/0000-0001-8040-2998
University of Copenhagen: Cytochrome P450 and Drug Metabolism

Lars Olsen

E-mail: lo@sund.ku.dk
ORCID: orcid.org/0000-0002-7607-7130
Work done at: University of Copenhagen
Present address: Novozymes A/S, Denmark

SMARTaox references

Marco Montefiori, Flemming Steen Jørgensen and Lars Olsen, Aldehyde Oxidase: Reaction Mechanism and Prediction of Site of Metabolism ACS Omega, 2017, 2, 4237-4244