Mechanism Study on the Interaction Between 2'-Hydroxy-2,4-dibromo Diphenyl Ethers and Human Serum Albumin Based on Spectroscopic Methods and Computional Simulations†

doi:10.7503/cjcu20141007

Abstract

Abstract:

The interaction between 2'-hydroxy-2,4-dibromo diphenyl ethers(2'-OH-BDE-7) and human serum albumin(HSA) was investigated with molecular docking, molecular dynamics simulation and spectroscopy techniques. The results of synchronous fluorescence spectroscopy indicated that the conformation of HSA was changed when 2'-OH-BDE-7 binding to HSA, which consistent with the results of molecular dynamics simulations. In addition, the results of fluorescence spectroscopy experiment showed that the intrinsic fluorescence quenching of HSA was reduced by 2'-OH-BDE-7. Static quenching and non-radiation energy transfer are the two main reasons leading to the fluorescence quenching of HSA by 2'-OH-BDE-7. In the process of binding, the entropy, the enthalpy and the Gibbs free energy were negative, which suggested that the interaction between 2'-OH-BDE-7 and HSA was driven mainly by hydrophobic forces and van de Waals forces. Finally, a similar conclusion was obtained from the competitive experiment and molecular docking, which shown 2'-OH-BDE-7 binded human serum albumin at site Ⅰ. Excellent agreement was founded between computer simulations results and spectral experiments to provide more information for the mechanism study on the interaction between 2'-OH-BDE-7 and HSA.

Key words: Human serum albumin, 2'-Hydroxy-2,4-dibromo diphenyl ether(2'-OH-BDE-7), Fluorescence spectrum, Molecular docking, Molecular dynamics simulation

CLC Number:

O641.3

TrendMD:

DONG Lu, YI Zhongsheng, WU Zhiwei, WANG Haiyang, ZHANG Aiqian. Mechanism Study on the Interaction Between 2'-Hydroxy-2,4-dibromo Diphenyl Ethers and Human Serum Albumin Based on Spectroscopic Methods and Computional Simulations^†[J]. Chem. J. Chinese Universities, 2015, 36(3): 516.

Figures/Tables 12

Fig.1 Root-mean-square displacement(RMSD)(A)and root mean square fluctuation(RMSF)(B) of free HSA and 2'-OH -BDE-7-HSA complexes from 10 ns of MD simulations

Fig.2 Rg of free HSA and 2'-OH-BDE-7-HSA complexes structural superposition of HSA at specific time from 10 ns MD MD time/ns: 0(red); 3(purple); 7(blue); 10(green).

Fig.3 Solvent accessible surface areas(SASA) for hydrophobic and hydrophilic moieties in the HSA and 2'-OH -BDE-7-HSA

Fig.4 Synchronous fluorescence spectra of 2'-OH-BDE-7-HSA (A) Δλ=15 nm; (B) Δλ=60 nm. cHSA=1.0 × 10-6 mol/L; 109c2'-OH-BDE-7/(mol·L-1): a—j. 0—9. Left arrow: blue shift; the maximum absorption wavelength move to short wavelength; number value: blue shift value; down arrow: intensity of quenching.

Fig.5 Fluorescence spectra of HSA in the presence of 2'-OH-BDE-7 Inset: Stern-Vomer curves at different temperatures.cHSA=1.0 × 10-6 mol/L; 109c2'-OH-BDE-7/(mol·L-1): a—j. 0—9. Left arrow: blue shift; the maximum absorption wavelength move to short wavelength; number value: blue shift value; down arrow: intensity of quenching.

Table 1 Quenching constant of 2'-OH-BDE-7-HSA interaction at different temperatures

T/K	10⁶K_SV/(L·mol^-1)	10^-14K_q/(L·mol^-1·s^-1)	r
291	4.58	4.58	0.9976
298	3.44	3.44	0.9970
310	2.71	2.71	0.9989

Fig.6 Fluorescence spectrum of HSA(a) and absorbance spectrum of 2'-OH-BDE-7(b) at 298 K cHSA=c2'-OH-BDE-7=1.0 × 10-7 mol/L.

Table 2 Docking results of Surflex-Dock at sites I and Ⅱ

Site	-lgK_d	ΔG/(kJ·mol^-1)	Hydrogen bond
Ⅰ	3.6267	-20.71	Ala291
Ⅱ	3.4474	-19.68

Fig.7 Molecular docking and detailed view of the interactions of 2'-OH-BDE-7 and HSA (A) 2'-OH-BDE-7 located at site Ⅰ of HSA; (B) HSA amino acids residues around 0.5 nm of 2'-OH-BDE-7; (C) electrostatic potential around 2'-OH-BDE-7; (D) combine distance between Trp214 and 2'-OH-BDE-7, r=0.427 nm.

Table 3 Binding constants(Ka), number of binding sites(n) of 2'-OH-BDE-7-HSA system at different temperatures

T/K	10⁷K_a/(L·mol^-1)	n	r
291	2.57	1.11	0.9959
298	1.98	1.11	0.9982
310	0.83	1.07	0.9994

Table 4 Thermodynamic parameters of 2'-OH-BDE-7-HSA system at different temperatures

T/K	ΔH/(kJ·mol^-1)	ΔG/(kJ·mol^-1)	ΔS/(J·mol^-1·K^-1)
291		-41.44
298	-45.79	-41.34	-14.92
310		-41.16

Table 5 Binding constant of experiments of 2'-OH-BDE-7-HSA system(T=298 K)

Compound	2'-OH-BDE-7-HSA	+Ibuprofen	+Warfarin
10⁶K_a/(L·mol^-1)	9.90	9.23	3.67

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