The interaction between organic phosphate ester and p53: an integrated experimental and in silico approach

Concerns have been raised in regards to the environmental impact of the more used organophosphate flame retardants (OPFRs). In this study, to better understand the relationship between molecular structural features of OPFRs and binding affinity for the tumor suppressor p53, an integrated experimental and in silico approach was used. From docking analysis, hydrogen bonding and hydrophobic interactions were found to be the dominant interactions, which implied the binding affinities of the compounds. The binding constants of 5 OPFRs were determined by surface plasmon resonance technology (SPR). Based on the observed interactions, appropriate molecular structural parameters were adopted to develop a quantitative structure-activity relationship (QSAR) model. The developed QSAR model had good robustness, predictive ability and mechanism interpretability. The interactions between the OPFRs and p53 (Ebinding) and the partition ability of the OPFRs into the bio-phase are main factors governing the binding affinities.