Application of molecular dynamic simulation on evaluating toxicity mechanisms of organophosphate esters to Photobacterium phosphoreum

Abstract

Organophosphate esters (OPEs) that are widely used as additives in industrial products have been monitored ubiquitously in environmental media. With the health hazards and ecological risks caused by OPEs being attracted more and more attention, screening toxicity mechanism was essential for risk assessment. In this study, Photobacterium phophorium was employed to test the acute toxicity of OPEs. Integrating toxicity test and molecular dynamics (MD) simulation, we calculated the binding affinity between OPEs and n-octanol (C8H18O)/ phospholipid bilayer (DPPC) to further explore the mechanism of toxicity. Good correlationship between the median effective concentration (EC50) of OPEs and binding affinity was found. Binding affinity of selected OPEs with the C8H18O/DPPC presented similar tendency. The mode of action (MOA) for OPEs to Photobacterium phophorium was shown that tris (1, 3-dichloro-2-propyl) phosphate (TDCP) belonged to reactive mechanism, triphenyl phosphate (TPhP) and tris (2-butoxyethyl) phosphate (TBEP) belonged to narcosis mechanism. It was proposed a creative method to quickly evaluate toxicity mechanisms of organophosphate esters by integrating the toxicity test and MD simulation, which could be an alternative methodology to obtain toxicity mechanism without using model organisms.