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Prediction of nanographene binding-scores to trout cellular receptors and cytochromes

Connolly, M.; Navas, J. M.; Coll, J.

2021-02-21 pharmacology and toxicology
10.1101/2021.02.20.432107 bioRxiv
Show abstract

To address the increasing concerns surrounding possible impacts of graphene-related materials on the aquatic environment, this study focused on computational predictions of binding between models of graphenes in the nm size range (nanographenes, nGs) and the aryl-hydrocarbon receptor (tAHR) and P450 cytochromes (tCYPs) of rainbow trout (Oncorhynchus mykiss). The tAHR plays a key role in the induction of detoxifying and early immune responses and tCYPs are essential for detoxifying planar hydrophobic chemicals such as nGs. After 3D modelling of those trout proteins, docking algorithms predicted the size-dependance profiles of nGs binding-scores to tAHR and tCYPs in the low nM range (high binding-affinities). Virtual oxidations of nGs to nGOs (carboxy-, epoxy-and/or hydroxy-oxidations) further lowered the corresponding binding-scores in level/type-oxidation manners. Among all the tCYPs, the tCYP3AR (the equivalent to human CYP3A4) was identified as a potential key interaction enzyme for nGs because of its lower binding-scores. These results implicate a possible processing pathway to be further probed through in vitro and in vivo experimentation. Together the information generated can be pivotal for the design of safer graphene-related materials for a variety of applications and help to understand their detoxification in aquatic vertebrates.

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