Unveiling the molecular interactions between bisphenol A and the cell surface Toll-like receptors: Implications for...

Microplastic pollution is an emerging threat to the human health. In nature, microplastics release several compounds of toxicological importance. Among them, bisphenol A (BPA), a widely used additive in plastic production, is an important one. Upon breakdown, microplastics release significant amounts of BPA in air, water, and soil. Humans may be exposed to BPA through nasal, oral, and dermal routes. BPA is linked to oxidative stress, physiological disturbance, and chronic diseases. Moreover, it may target the immune system. Toll-like receptors (TLRs) are important mediators of both innate and adaptive immunity and recognize microbial signature molecules to trigger signaling cascades employed in anti-microbial defense mechanism. Inhibition of TLR-mediated signaling can result in compromised immunity. Hence, the present work aims to investigate the inhibitory potential of BPA against cell surface TLRs. For this study, a molecular docking approach using the AutoDock vina algorithm was employed to analyze the docking potential of BPA with the surface-associated TLRs. Results have revealed that BPA binds to TLR1, TLR2, TLR4, TLR5, and TLR6 with affinity ranging from -4.3 to -7.3 kcal/mol. Structural analyses of the docked complexes have suggested that BPA binds to TLR through conventional H-bonds. Van der Waals and other hydrophobic interactions further stabilized the docked complexes. Notably, C-H bonds were also apparent in some docked conformations. Hence, results of the present study equivocally suggest that BPA can potentially bind to the cell surface TLRs through various bonds and interactions. Such interactions may modulate TLR-mediated signaling and immunity in organisms.