The molecular mechanisms of TRß receptor interaction with polychlorinated biphenyls: A multispectral and computational exploration.

The thyroid hormone (TH) system is susceptible to the toxic effects of polychlorinated biphenyls (PCBs). Pollutants may disrupt the TH system by binding to serum TH transport proteins or interacting with thyroid hormone receptors (TRs) in target cells. However, the molecular mechanism of interaction with the Thyroid Hormone Receptor Beta (TRß) is not fully understood. This study employed fluorescence, UV-visible absorption, three-dimensional fluorescence, and Fourier-transform infrared spectroscopy, along with molecular docking and molecular dynamics simulations, to investigate the interaction between TRß and PCBs. Moreover, molecular docking and fluorescence resonance energy transfer (FRET) findings suggest that TRß and PCBs underwent resonance energy transfer consistent with Förster's theory. The root mean square deviation (RMSD) and docking outcomes indicate that the TRß-PCB29 complex exhibited optimal structural stability. Thus, the study concludes that integrating spectroscopic data with molecular docking is essential for a comprehensive analysis. Further analysis of intermolecular interactions using quantum chemistry and reduced density gradient analysis (RDG) analysis revealed that van der Waals forces are the primary drivers of PCBs to TRß.

Binding Mechanism of Nitro Musks to Human Lactoferrin: Multispectral Approach, Docking and Molecular Dynamics Simulation.

Nitro musks are highly bioaccumulative and potentially carcinogenic, commonly used as additives in fabric softeners, detergents, and other household products. Furthermore, these substances have been detected in breast milk and human adipose tissue, posing a risk of direct exposure to pregnant women and infants. Human lactoferrin (HLF) is abundant in colostrum, and plays an important role in the non-specific immune system of the human body. In this study, the mechanisms of action of two nitro musk compounds, typical examples of synthetic musks, with HLF were investigated using molecular docking, dynamics simulation and multispectral methods. The fluorescence findings demonstrated that nitro musks quenched the intrinsic fluorescence of human lactoferrin through static quenching. Thermodynamic analysis of the binding parameters suggested that hydrophobic interactions acted synergistically in the formation of the complex. Moreover, analyses utilizing multispectral techniques, such as Fourier transform infrared (FTIR) spectroscopy, validated that the microenvironment and structure of HLF were altered in the presence of nitro musks. Finally, molecular docking and molecular dynamics simulations were employed to explore the specific binding mode of nitro musks with HLF and to assess the stability of the complex. These findings may provide a reference for assessing health risks to pregnant women and infants.

Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple Spectral Methods.

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human physiological conditions (pH = 7.4), a combination of multiple spectroscopic techniques and computational simulations was employed to investigate the impact of perfluorinated compounds (PFCs) on the G protein-coupled estrogen receptor (GPER). Additionally, the research focused on exploring the binding modes and toxicological mechanisms between PFCs and GPER at the molecular level. All three perfluorinated sulfonic acids (PFSAs) can induce quenching of GPER fluorescence through static quenching and non-radiative energy transfer. Steady-state fluorescence calculations at different temperatures revealed apparent binding constants in the order of 106, confirming a strong binding affinity between the three PFSAs and GPER. Molecular docking studies indicated that the binding sites of PFSAs are located within the largest hydrophobic cavity in the head region of GPER, where they can engage in hydrogen bonding and hydrophobic interactions with amino acid residues within the cavity. Fourier transform infrared spectroscopy, three-dimensional fluorescence, and molecular dynamics simulations collectively indicate that proteins become more stable upon binding with small molecules. There is an overall increase in hydrophobicity, and alterations in the secondary structure of the protein are observed. This study deepens the comprehension of the effects of PFCs on the endocrine system, aiding in evaluating their potential impact on human health. It provides a basis for policy-making and environmental management while also offering insights for developing new pollution monitoring methods and drug therapies.

Anthracene-based dual channel donor-acceptor triazine-containing covalent organic frameworks for superior photoelectrochemical sensing.

Covalent organic frameworks (COFs) exhibit excellent photoelectrically active structures and serve as channels for photon capture and charge carrier transport. However, their relatively high charge-carrier recombination rates and lack of specific recognition sites limit their application in photoelectrochemical sensing. This paper reports a functionalized donor-acceptor (D-A) COF comprising electron-rich polycyclic aromatic moieties and electron-deficient triazines (Tz) incorporating boronic acid through ligand exchange. The number of aromatic rings in the polycyclic aromatic moiety is crucial for establishing an efficient D-A system within COF. In the absence of an external electron donor, the anthracene-based COF exhibited a five-fold enhancement in photocurrent compared to the naphthalene-based COF. The resulting anthracene-based D-A COF exhibited enhanced orbital overlap and electron push-pull interactions, facilitating more effective charge separation. Furthermore, introducing boronic acid enabled the selective enrichment of low-concentration external electron donors, such as dopamine, in the inner Helmholtz plane. This ingenious approach establishes a unique dual-channel D-A system that allows direct measurement of dopamine in serum. Under optimized conditions, the test platform achieves good correspondence for dopamine at 1 to 100 nM and 0.5 to 100 µM with a detecting limit of 0.36 nM (3σ/S, n = 11). This strategy introduces a novel dimension to photoelectrochemical sensing, focusing on the effect of spatial separation between the external electron donor and the photoelectrode interface that intricately shapes the behavior and enhances the performance of the photoelectric system.

Exploring the mechanism of interaction between TBG and halogenated thiophenols: Insights from fluorescence analysis and molecular simulation.

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.

Thyroid hormone transporters binding affinity of methoxypoly chlorinated biphenyls: Insights from molecular simulations and fluorescence competitive binding experiment.

Triiodothyronine (T3) and thyroxine (T4) are essential for regulating cell metabolic rate and promoting the development and differentiation of brain tissue, especially in fetuses and newborns. In particular, it has been proved that MeO-PCBs have high binding to thyroid hormone transporters and can competitively bind to thyroid carrier proteins, thus destroying the transport of the thyroid hormone. Fluorescence competition binding experiments and docking results showed that the binding affinity decreased with the increase in number of chlorine atoms of MeO-PCBs. The interaction mechanism of MeO-PCBs with thyroid transporter (TTR) and thyroid binding globulin (TBG) was compared by computational simulation and the binding free energies were calculated by the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Electrostatic potential analysis, Hirshfeld surface analysis and electron density difference maps confirmed the existence of electrostatic interactions. Secondly, noncovalent interaction (NCI) analysis further indicated that the main driving force for the combination of MeO-PCBs to TTR and TBG were electrostatic interaction and van der Waals interaction. The conformational changes of the protein after binding were studied by a molecular dynamic simulation.

Interactions between polycyclic musks and human lactoferrin: Multi-spectroscopic methods and docking simulation.

Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-γ-2-benzopyrane; HHCB) and Tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene; AHTN) are "pseudo-persistent" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF-HHCB, HLF-AHTN complex, and accompanied by non-radiative energy transfer and that 1:1 complexes form through interaction forces. Time-resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three-dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet-visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother-and-child health risk assessments.

Investigations on the binding properties of hydroxylated polybrominated diphenyl ethers with lysozyme using the multispectral techniques and molecular modeling.

As a kind of phenolic chemical with endocrine disrupting potency, hydroxylated polybrominated diphenyl ethers (OH-PBDEs) cause a latent threat to human health from their residue in the environment. Their binding efficiency with lysozyme (LYSO) was studied by molecular simulation combined with fluorescence, UV-vis absorption and circular dichroism (CD), so as to assess their toxicity at the molecular level. Molecular docking data indicate that van der Waals force is the principal interaction force between OH-PBDEs and LYSO. The binding site for 5'-OH-BDE-25 in LYSO is ascertained as the active site, which interaction with the TRP63 and TRP108 residues of LYSO to take shape a strong face-to-face stacked rank (F-shaped). Both 4'-OH-BDE-99 and 3'-OH-BDE-154 display a certain degree of deviation from the active site. Nevertheless, their F-shaped interaction with TRP63 conduce to bind LYSO and stabilize the docking conformation. Combined with dynamics simulation and spectral analysis, the secondary structure of LYSO can be induced by the three kinds of OH-PBDEs. CD spectrum shows that the combination of LYSO and OH-PBDEs will make α- Helix content increased. The combination of OH-PBDEs and LYSO touch upon a static quenching mechanism as a result of steady state fluorescence. The energy decomposition analysis exhibited that LYSO-OH-PBDEs binding site was stable by van der Waals and hydrophobic interaction. As enzyme activity experiments demonstrate that OH-PBDEs can inhibit the activity of LYSO, which is helpful to clarify the molecular toxicity mechanism of OH-PBDEs.

Insight on the microscopic binding mechanism of bisphenol compounds (BPs) with transthyretin (TTR) based on multi-spectroscopic methods and computational simulations.

Thyroid hormones are involved in numerous physiological processes as regulators of metabolism, regulating organ growth, and mental state. Bisphenol compounds (BPs) are recognized as chemicals that interfere with endocrine balance. Because BPs have a similar structure to thyroxine, they can compete for binding to thyroid protein and disrupt the normal physiological activity of the thyroid system. In this study, three typical bisphenol compounds were selected to explore the interaction between BPs and TTR by computer simulations and multi-spectroscopic methods. The results revealed that BPs quenched the endogenous fluorescence of TTR via the combination of static quenching and non-radiative energy transfer, and the van der Waals forces and hydrogen bonding played a synergistic role in the binding process of BPs and TTR. Furthermore, the three-dimensional fluorescence spectroscopy, UV-vis spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy, which were employed to determine the conformation of protein, revealed that binding of BPs with TTR could induce conformational changes in TTR. In addition, the binding sites and the residues surrounding the BPs within the TTR were determined through molecular docking and molecular dynamics simulation. Therefore, this work provides new insights into the interaction between BPs and TTR to evaluate the potential toxicity of BPs.

Interaction between laccase and diethylstilbestrol based on multispectral and chromatography analyses.

Diethylstilbestrol (DES) is a synthetic form of oestrogen that does not easily degrade in the environment and can be harmful to human health. Herein, the mechanism of the interaction between laccase and DES was investigated by various spectroscopic means and high-performance liquid chromatography (HPLC). The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of laccase by DES was due to a static quenching, forming a binding site. According to the Förster non-radiative energy transfer theory (FRET), the action distance R0 between DES and laccase was 4.708 nm, r was 5.81 nm, and the energy transfer efficiency E was 22.08%, respectively. Both UV-Vis absorption spectra and FT-IR spectra indicated changes in the conformation and surroundings of the enzyme and changed in the secondary structure of laccase. Multispectral synthesis showed that the interaction of laccase with DES caused a change in the secondary structure of laccase. The degradation experiments showed that laccase could degrade DES, and the DES content decreased with time. This study provides a new theoretical basis and experimental method for further research on the reaction mechanism of the laccase degradation of DES. It may also provide a reference basis for human biological and environmental safety evaluations.