Exploring the binding mechanism of parabens to transthyretin: An integrated analysis using multi-spectral and computational simulation techniques

Thyroid hormones, secreted by the thyroid gland, are critical for regulating physiological processes such as growth and development, metabolism, metabolic homeostasis, and cardiovascular function. These hormones regulate metabolic rate, promote skeletal and nervous system maturation, and maintain cardiac function. However, endocrine disruptors can compete for binding to transthyretin (TTR), a transport protein for thyroid hormones. This study examines the mechanisms of interaction between endocrine disruptors and TTR, focusing on parabens (PBs). We used fluorescence, UV–visible absorption, 3D fluorescence spectroscopy, and molecular dynamics simulations to investigate the molecular interactions between PBs and TTR. Fluorescence spectroscopy demonstrated high binding affinity between PBs to TTR, as evidenced by significant static quenching of TTR’s intrinsic fluorescence. UV–vis absorption and 3D fluorescence spectra showed that PBs altered TTR’s microenvironment, with butylparaben (BuPB) causing the most pronounced quenching effect, confirmed by quantum chemical analysis. Molecular docking and molecular dynamics simulations revealed the optimal binding modes and stability of PBs-TTR complex. Notably, BuPB exhibited the lowest binding free energy and highest stability, indicating stronger interactions with TTR than other PBs. These findings reveal the mechanism by which PBs interfere with TTR function, potentially disrupting thyroid hormone transport.