Determination of the binding affinities of OPEs to integrin αvß3 and elucidation of the underlying mechanisms via a competitive binding assay, pharmacophore modeling, molecular docking and QSAR modeling.

ABSTRACT

Organophosphate esters (OPEs) can cause adverse biological effects through binding to integrin αvß3. However, few studies have focused on the binding activity and mechanism of OPEs to integrin αvß3. Herein, a comprehensive investigation of the mechanisms by which OPEs bind to integrin αvß3 and determination of the binding affinity were conducted by in vitro and in silico approaches competitive binding assay as well as pharmacophore, molecular docking and QSAR modeling. The results showed that all 18 OPEs exhibited binding activities to integrin αvß3; moreover, hydrogen bonds were identified as crucial intermolecular interactions. In addition, essential factors, including the -P = O structure of OPEs, key amino acid residues and suitable cavity volume of integrin αvß3, were identified to contribute to the formation of hydrogen bonds. Moreover, aryl-OPEs exhibited a lower binding activity with integrin αvß3 than halogenated- and alkyl-OPEs. Ultimately, the QSAR model constructed in this study was effectively used to predict the binding affinity of OPEs to integrin αvß3, and the results suggest that some OPEs might pose potential risks in aquatic environments. The results of this study comprehensively elucidated the binding mechanism of OPEs to integrin αvß3, and supported the environmental risk management of these emerging pollutants.