Endocrine disruption by Bisphenol A, polychlorinated biphenyls and polybrominated diphenyl ether, in zebra fish (Danio rerio) model: an in silico approach.

Endocrine disrupting chemicals may induce adverse health effects in humans and wildlife. Recent studies demonstrate that endocrine disrupting chemicals like Bisphenol A (BPA), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDE) affect the reproductive characters shared by wide range of creatures including fish. An attempt was made to evaluate the toxicity of these chemicals on the vitellogenin protein of zebra fish (Danio rerio) using in silico approach. The protein structure of zebra fish vitellogenin was predicted using homology modelling, and the stereochemical quality of the model was validated by Ramachandran plot. The 3-D structure of vitellogenin was docked with the aforementioned chemicals that have demonstrated endocrine-disrupting activity. The pair-wise alignments between vitellogenin with phosvitin, lipovitellin-2 and YGP40 obtained by CLUSTALW alignment suggest that the vitellogenin contained lipovitellin-2- phosvitin- and YGP40-related amino acid sequences. Based on the prediction of CASTp and CLUSTALW, BPA and PCB predominantly interacted with lipovitellin-2 site of the protein, while PBDE interacts predominantly with the YGP40 site of the vitellogenin protein. The results indicate that the endocrine-disrupting chemicals (BPA, PCB and PBDE) dock with the vitellogenin cleavage sites lipovitellin-2 and YGP40 that play a crucial role in lipid-protein complex formation in the egg yolk. We hypothesize that these chemicals could potentially impair the egg yolk formation and eventually impact the zebra fish population which occupies an important niche among testing models used in drug discovery and related toxicity studies.