The mechanism and conformational changes of polybrominated diphenyl ethers to TTR by fluorescence spectroscopy, molecular simulation, and quantum chemistry

The Analyst ◽  
2018 ◽  
Vol 143 (19) ◽  
pp. 4662-4673
Author(s):  
Jie Xu ◽  
Yuchen Wei ◽  
Wu Yang ◽  
Lulu Yang ◽  
Zhongsheng Yi
Keyword(s):  
Free Energy ◽  
Amino Acid ◽  
Molecular Modeling ◽  
Fluorescence Spectroscopy ◽  
Quantum Chemistry ◽  
Conformational Changes ◽  
Polybrominated Diphenyl Ethers ◽  
Energy Contribution ◽  
Diphenyl Ethers ◽  
Free Energy Contribution

Free energy contribution of amino acid LYS (B and D chains) and PDBEs was analyzed combining quantum chemistry and molecular modeling.

scholarly journals Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

2008 ◽  
Vol 5 (29) ◽  
pp. 1391-1408 ◽  
Author(s):  
Gabriel M Altschuler ◽  
Keith R Willison
Keyword(s):  
Free Energy ◽  
Essential Role ◽  
Cytoskeletal Protein ◽  
Type I ◽  
Folding Intermediate ◽  
Energy Contribution ◽  
Nucleotide Hydrolysis ◽  
Chaperonin Groel ◽  
Free Energy Contribution ◽  
Bacterial Type

A free-energy-based approach is used to describe the mechanism through which chaperonin-containing TCP-1 (CCT) folds the filament-forming cytoskeletal protein actin, which is one of its primary substrates. The experimental observations on the actin folding and unfolding pathways are collated and then re-examined from this perspective, allowing us to determine the position of the CCT intervention on the actin free-energy folding landscape. The essential role for CCT in actin folding is to provide a free-energy contribution from its ATP cycle, which drives actin to fold from a stable, trapped intermediate I 3 , to a less stable but now productive folding intermediate I 2 . We develop two hypothetical mechanisms for actin folding founded upon concepts established for the bacterial type I chaperonin GroEL and extend them to the much more complex CCT system of eukaryotes. A new model is presented in which CCT facilitates free-energy transfer through direct coupling of the nucleotide hydrolysis cycle to the phases of actin substrate maturation.

scholarly journals A Fluorescence-Based Method for Rapid and Direct Determination of Polybrominated Diphenyl Ethers in Water

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Huimei Shan ◽  
Chongxuan Liu ◽  
Zheming Wang ◽  
Teng Ma ◽  
Jianying Shang ◽  
...  
Keyword(s):  
Fluorescence Spectroscopy ◽  
Polybrominated Diphenyl Ethers ◽  
Environmental Variables ◽  
Fluorescence Spectra ◽  
Direct Determination ◽  
Spectral Signal ◽  
Diphenyl Ethers ◽  
Spectral Profiles ◽  
Bde 209

A new method was developed for rapid and direct measurement of polybrominated diphenyl ethers (PBDEs) in aqueous samples using fluorescence spectroscopy. The fluorescence spectra of tri- to deca-BDE (BDE 28, 47, 99, 153, 190, and 209) commonly found in environment were measured at variable emission and excitation wavelengths. The results revealed that the PBDEs have distinct fluorescence spectral profiles and peak positions that can be exploited to identify these species and determine their concentrations in aqueous solutions. The detection limits as determined in deionized water spiked with PBDEs are 1.71–5.82 ng/L for BDE 28, BDE 47, BDE 190, and BDE 209 and 45.55–69.95 ng/L for BDE 99 and BDE 153. The effects of environmental variables including pH, humic substance, and groundwater chemical composition on PBDEs measurements were also investigated. These environmental variables affected fluorescence intensity, but their effect can be corrected through linear additivity and separation of spectral signal contribution. Compared with conventional GC-based analytical methods, the fluorescence spectroscopy method is more efficient as it only uses a small amount of samples (2–4 mL), avoids lengthy complicated concentration and extraction steps, and has a low detection limit of a few ng/L.

scholarly journals Understanding the microscopic binding mechanism of hydroxylated and sulfated polybrominated diphenyl ethers with transthyretin by molecular docking, molecular dynamics simulations and binding free energy calculations

2017 ◽  
Vol 13 (4) ◽  
pp. 736-749 ◽  
Author(s):  
Huiming Cao ◽  
Yuzhen Sun ◽  
Ling Wang ◽  
Chunyan Zhao ◽  
Jianjie Fu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Polybrominated Diphenyl Ethers ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Binding Mechanism ◽  
Diphenyl Ethers ◽  
Binding Free Energy Calculations ◽  
Dynamics Simulations

The binding of TTR with sulfated-PBDEs and OH-PBDEs shows different molecular recognition mechanisms.

scholarly journals Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1)

2021 ◽  
Author(s):  
Shashank Pant ◽  
Qianyi Wu ◽  
Renae M Ryan ◽  
Emad Tajkhorshid
Keyword(s):  
Free Energy ◽  
Amino Acid ◽  
Conformational Changes ◽  
Large Scale ◽  
Excitatory Amino Acid ◽  
Free Energy Calculations ◽  
Amino Acid Transporters ◽  
Coupled Transport ◽  
Energy Calculations ◽  
Transport Cycle

Excitatory amino acid transporters (EAATs) are glutamate transporters that belong to the solute carrier 1A (SLC1A) family. They couple glutamate transport to the co-transport of three sodium (Na+) ions and one proton (H+) and the counter-transport of one potassium (K+) ion. In addition to this coupled transport, binding of substrate and Na+ ions to EAATs activates a thermodynamically uncoupled chloride (Cl-) conductance. Structures of SLC1A family members have revealed that these transporters use a twisting elevator mechanism of transport, where a mobile transport domain carries substrate and coupled ions across the membrane, while a static scaffold domain anchors the transporter in the membrane. We have recently demonstrated that the uncoupled Cl- conductance is activated by the formation of an aqueous pore at the domain interface during the transport cycle in archaeal GltPh. However, a pathway for the uncoupled Cl- conductance has not been reported for the EAATs and it is unclear if such a pathway is conserved. Here, we employ all-atom molecular dynamics (MD) simulations combined with enhanced sampling, free-energy calculations, and experimental mutagenesis to approximate large-scale conformational changes during the transport process and identified a Cl- conducting conformation in human EAAT1. We were able to extensively sample the large-scale structural transitions, allowing us to capture an intermediate conformation formed during the transport cycle with a continuous aqueous pore at the domain interface. The free-energy calculations performed for the conduction of Cl- and Na+ ions through the captured conformation, highlight the presence of two hydrophobic gates which control the selective movement of Cl- through the aqueous pathway. Overall, our findings provide insights into the mechanism by which a human glutamate transporter can support the dual functions of active transport and passive Cl- permeation and confirming the commonality of this mechanism in different members of the SLC1A family.

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