The binding characteristics of organophosphate and thyroid transporter: Insight from multispectral and molecular simulations

Thyroid hormones are essential for mammalian development, tissue differentiation and metabolic balance regulation. T4 is the most abundant thyroid hormone secreted by the thyroid gland. Thyrotropin transporter (TTR) transports approximately 15 % of T4 in human plasma. The interaction between organophosphate (OPEs) and TTR was studied using multispectral techniques and computer simulations. Fluorescence experiment results demonstrate that the quenching constant declines with increasing temperature, suggesting that OPEs quench TTR's intrinsic fluorescence via a static quenching mechanism. The binding constant for OPEs to TTR is approximately 1.0 x 10-6 L & sdot;mol-1, indicating strong binding affinity. Comparison of the binding constants for OPEs molecules with various structures at 298 K reveals that benzene ring and halogen substitutions enhance their binding to TTR. An increasing number of carbon chain substitutions intensifies the effect on TTR. From a thermodynamic perspective, the negative binding free energy values at various temperatures indicate a spontaneous binding process. Electrostatic forces, hydrogen bonds and van der Waals interactions are the primary stabilizing forces of the complex, as confirmed by molecular docking and binding free energy calculations. The highest binding free energy value for the complex of TBOEP with TTR is-548.46 kcal/mol. Molecular docking indicates that OPEs bind within TTR's hydrophobic cavity, interacting via amino acid residues for hydrogen bonds and hydrophobic interactions. Three-dimensional fluorescence and UV-vis absorption spectra reveal that OPEs addition alters the TTR's binding site microenvironment and induces conformational changes.