Figure 3.

A molecular modeling study to assess the docked complex of bisphenol A (BPA) with Cx43-based gap junction communication channel. (A) Topographic view of the Cx43-gap junction protein complex with BPA. (B) Side view of the Cx43-gap junction protein complex with BPA. (C) Ball and stick model for the interaction residues and secondary structure representation for protein between BPA and Cx43. Molecular docking of bisphenol A into Cx43 shows formation of strong interactions by making two hydrogen bonds in the complex. The side chain oxygen atom of Asp3 (D3, Chain A) and backbone nitrogen atoms of Gly2 (G2, Chain A) were involved in hydrogen bond formation at the bond distance of 1.587 Å and 1.748 Å, respectively. In addition to these residues, Gly2 (G2, Chain B and F), Asp3 (D3, Chain B–F), Trp4 (W4, Chain A and F), Ser5 (S5, Chain F), Ala6 (A6, Chain B, E and F) and Leu7 (L7, Chain B and C) were involved in non-bonded interactions, such as van der Waals forces. Asp3 (D3) and Trp4 (W4) are the major residues involved in the interaction in this docked complex. Glide docking score of the complex was −4.07 kcal/mol. The binding site surface and ligand surface area of the docked complex were 1494.841 Å and 253.687 Å, respectively. It is noted that the residues of N-terminal helix (NTH) in Cx43 alone was involved in the interactions with BPA. The compound BPA appears to occupy largest binding site surface area in the Cx43 and can block the channel based on the molecular modeling, which is consistent with recent findings using a functional GJ communication assay.⁴⁰