Predicting sites of cytochrome P450-mediated hydroxylation applied to CYP3A4 and hexabromocyclododecane
- This article describes a simple and quick in silico method for the prediction of cytochrome P450 (CYP)-mediated hydroxylation of drug-like compounds. Testosterone and progesterone, two known substrates of CYP3A4, are used to test the method. Further, we apply the procedure to predict sites of hydroxylation of isomers of the flame retardant hexabromocyclododecane by CYP3A4. Within the method, the compound is rotated in the binding pocket of the cytochrome, so that each hydrogen under consideration is placed near the active centre. Afterwards, short molecular dynamics simulations are provided for each step of the rotation. All steps of the simulation are compared concerning the distances between the hydrogens and the active centre and the corresponding energies. The computational results correlate well with experimental results.
Autor*innen: | O. Scharkoi, Roland BeckerORCiD, Susanne Esslinger, M. Weber, Irene Nehls |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | Molecular simulation |
Jahr der Erstveröffentlichung: | 2015 |
Verlag: | Gordon and Breach |
Verlagsort: | New York, NY |
Jahrgang/Band: | 41 |
Ausgabe/Heft: | 7 |
Erste Seite: | 538 |
Letzte Seite: | 546 |
Freie Schlagwörter: | Cytochrome P450; Hydroxylation; Metabolism of HBCD; Predicting sites of metabolism |
DOI: | 10.1080/08927022.2014.898845 |
ISSN: | 0892-7022 |
ISSN: | 1029-0435 |
Verfügbarkeit des Dokuments: | Datei im Netzwerk der BAM verfügbar ("Closed Access") |
Datum der Freischaltung: | 20.02.2016 |
Referierte Publikation: | Ja |
Datum der Eintragung als referierte Publikation: | 07.04.2014 |