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Interactions of 2-phenyl-benzotriazole xenobiotic compounds with human Cytochrome P450-CYP1A1 by means of docking, molecular dynamics simulations and MM-GBSA calculations

dc.contributor.authorMena-Ulecia K.
dc.contributor.authorMacLeod-Carey D.
dc.date.accessioned2020-09-02T22:22:54Z
dc.date.available2020-09-02T22:22:54Z
dc.date.issued2018
dc.identifier10.1016/j.compbiolchem.2018.04.004
dc.identifier.citation74, , 253-262
dc.identifier.issn14769271
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5292
dc.description2-phenyl-benzotriazole xenobiotic compounds (PBTA-4, PBTA-6, PBTA-7 and PBTA-8) that were previously isolated and identified in waters of the Yodo river, in Japan (Nukaya et al., 2001; Ohe et al., 2004; Watanabe et al., 2001) were characterized as powerful pro-mutagens. In order to predict the activation mechanism of these pro-mutagens, we designed a computational biochemistry protocol, which includes, docking experiments, molecular dynamics simulations and free energy decomposition calculations to obtain information about the interaction of 2-phenyl-benzotriazole molecules into the active center of cytochrome P450-CYP1A1 (CYP1A1). Molecular docking calculations using AutoDock Vina software shows that PBTAs are proportionally oriented in the pocket of CYP1A1, establishing π-π stacking attractive interactions between the triazole group and the Phe224, as well as, the hydrogen bonds of the terminal NH2 over the benzotriazole units with the Asn255 and Ser116 amino acids. Molecular dynamics simulations using NAMD package showed that these interactions are stable along 100.0 ns of trajectories. Into this context, free binding energy calculations employing the MM-GBSA approach, shows that some differences exists among the interaction of PBTAs with CYP1A1, regarding the solvation, electrostatic and van der Waals interaction energy components. These results suggest that PBTA molecules might be activated by CYP1A1. Thus, enhancing their mutagenicity when compared with the pro-mutagen parent species. © 2018 Elsevier Ltd
dc.language.isoen
dc.publisherElsevier Ltd
dc.subject2-Phenyl-benzotriazole
dc.subjectMM-GBSA
dc.subjectMolecular docking
dc.subjectMolecular dynamics simulations
dc.subjectBinding energy
dc.subjectComplexation
dc.subjectComputational chemistry
dc.subjectFree energy
dc.subjectHydrogen bonds
dc.subjectMolecular modeling
dc.subjectMolecules
dc.subjectMutagenesis
dc.subjectMutagens
dc.subjectVan der Waals forces
dc.subject2-Phenyl-benzotriazole
dc.subjectActivation mechanisms
dc.subjectAttractive interactions
dc.subjectComputational biochemistries
dc.subjectMM-GBSA
dc.subjectMolecular docking
dc.subjectMolecular dynamics simulations
dc.subjectVan der Waals interaction energy
dc.subjectMolecular dynamics
dc.subject2-(2-(acetylamino)-4-(bis(2-hydroxyethyl)amino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole
dc.subject2-(2-(acetylamino)-4-(diallylamino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole
dc.subject2-(2-(acetylamino)-4-(diethylamino)-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole
dc.subject2-(2-(acetylamino)-4-amino-5-methoxyphenyl)-5-amino-7-bromo-4-chloro-2H-benzotriazole
dc.subjectaniline derivative
dc.subjectcytochrome P450 1A1
dc.subjecttriazole derivative
dc.subjectxenobiotic agent
dc.subjectchemical structure
dc.subjectchemistry
dc.subjecthuman
dc.subjectmetabolism
dc.subjectmolecular docking
dc.subjectmolecular dynamics
dc.subjectthermodynamics
dc.subjectAniline Compounds
dc.subjectCytochrome P-450 CYP1A1
dc.subjectHumans
dc.subjectMolecular Docking Simulation
dc.subjectMolecular Dynamics Simulation
dc.subjectMolecular Structure
dc.subjectThermodynamics
dc.subjectTriazoles
dc.subjectXenobiotics
dc.titleInteractions of 2-phenyl-benzotriazole xenobiotic compounds with human Cytochrome P450-CYP1A1 by means of docking, molecular dynamics simulations and MM-GBSA calculations
dc.typeArticle


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