多溴联苯醚与人血清白蛋白相互作用的表面等离子体共振及分子对接

doi:10.7503/cjcu20200270

摘要/Abstract

摘要：

采用表面等离子体共振(SPR)技术, 在模拟生理条件下实时动态研究了8种典型多溴联苯醚(PBDEs)与人血清白蛋白(HSA)相互作用的动力学和热力学行为. 通过分子对接模拟研究了PBDEs与HSA相互作用的分子机制, 探讨了不同PBDEs与蛋白的结合模式及作用力. 动力学实验结果表明, PBDEs中溴原子的个数和取代位置对相互作用有规律性的影响. 溴原子通过改变PBDEs分子与HSA作用过程中的解离速率来影响其亲和力, 溴原子个数越多, PBDEs与HSA作用的亲和力越强; 而取代基位置则影响PBDEs与HSA作用结合速率的快慢, 同分异构体中间位取代溴的亲和力大于邻位取代溴. 分子对接结果显示, 8种PBDEs主要结合于HSA的Site I位点, 但结合位点周边氨基酸残基类型的差异影响了结合力. 范德华力和氢键对结合能的贡献远大于静电力.

关键词: 多溴联苯醚, 人血清白蛋白, 相互作用, 表面等离子体共振, 动力学分析, 分子对接

Abstract:

The interactions between eight polybrominated diphenyl ethers(PBDEs) and human serum albumin(HSA) were studied by using surface plasmon resonance(SPR) and molecular docking technologies. The results of SPR kinetic analysis showed that both the number and substitution position of bromine on PBDEs had regular influences on the interaction. Bromine atoms mainly affected the dissociation rate of interaction, cau- sing the affinity of PBDE and HSA to increase with the number of bromine atoms. The position of bromine on PBDEs mainly affected the association rate of interaction, resulting in the high affinity of m-substituted PBDE and HSA than that of o-substituted PBDE in isomers. The results of molecular docking indicated although all PBDEs were mainly bound to site I of HSA, the difference of amino acid residues around the binding site affected the binding ability. The van der Waals force and hydrogen bond force had greater contribution to binding free energy than electrostatic force. The experimental datum of SPR were in good agreement with the results of computer simulation.

Key words: Polybrominated diphenyl ethers(PBDEs), Human serum albumin(HSA), Interaction, Surface plasmon resonance(SPR), Kinetics analysis, Molecular docking

中图分类号:

O641.3

TrendMD:

张爱芹, 王嫚, 申刚义, 金军. 多溴联苯醚与人血清白蛋白相互作用的表面等离子体共振及分子对接. 高等学校化学学报, 2020, 41(9): 2054.

ZHANG Aiqin, WANG Man, SHEN Gangyi, JIN Jun. Interactions Between Polybrominated Diphenyl Ethers and Human Serum Albumin Using SPR and Molecular Docking. Chem. J. Chinese Universities, 2020, 41(9): 2054.

图/表 6

参考文献 25

1	Hale R. C., La Guardia M. J., Harvey E. P., Gaylor M. O., Mainor T. M., Duff W. H., Nature, 2001, 412(6843), 140―141
2	Chen Y. J., Zhang A. Q., Li H. X., Peng Y., Lou X. Y., Liu M. Y., Hu J. C., Liu C., Wei B. K., Jin J., Chemosphere, 2020, 247, 125950―125960
3	Qiu Y. W., Qiu H. L., Zhang G., Li J., Sci. Total Environ., 2019, 651, 1788―1795
4	Wang Y. X., Jiang G. B., Chin. Sci. Bull., 2008, 53, 129―140(王亚韡, 江桂斌. 科学通报, 2008, 53, 129―140)
5	Rodriguez E. A., Li X., Lehmler H. J., Robertson L. W., Duffe M. W., Environ. Sci. Technol., 2016, 50, 5320―5327
6	Cao J., Lin Y., Guo L. H., Zhang A. Q., Wei Y., Yang Y., Toxicology, 2010, 277, 20―28
7	Cao H., Sun Y., Wang L., Zhao C., Fu J., Zhang A., Mol. Biosyst.,2017, 13(4), 736―749
8	Ren X. M., Guo L. H., Environ. Sci. Technol., 2012, 46, 4633―4640
9	Równicka⁃Zubik J., Sułkowsk L., Toborek M., Spectrochim Acta A: Mol. Biomol. Spectrosc., 2014, 24, 632―637
10	Dong L., Yi Z. S., Wu Z. W., Wang H. Y., Zhang A. Q., Chem. J. Chinese Universities, 2015, 36(3), 516―522(董露, 易忠胜, 伍智蔚, 王海洋, 张爱茜. 高等学校化学学报, 2015, 36(3), 516―522)
11	Tan S. W., Chi Z. W., Shan Y., Wen Z. Z., Li W. G., Environ. Toxicol. Pharmacol.,2017, 54, 34―39
12	Zhang A. Q., Wang M., Zhang H., Shen G. Y., Jin J., Chem. Bull., 2018, 81, 21―28(张爱芹, 王嫚, 张辉, 申刚义, 金军. 化学通报, 2018, 81, 21―28)
13	Shen G. Y., Gao Y., Dai D. S., Cui J., Liu Y. M., Pei L. P., Chem. J. Chinese Universities, 2011, 32(8), 1709―1713(申刚义, 高妍, 戴东升, 崔箭, 刘裕明, 裴凌鹏. 高等学校化学学报, 2011, 32(8), 1709―1713)
14	Shen G. Y., Gao Y., Zhang A. Q., Cui J., Dai D. S., Chem. J. Chinese Universities, 2015, 36(5), 881―885(申刚义, 高妍, 张爱芹, 崔箭, 戴东升. 高等学校化学学报, 2015, 36(5), 881―885)
15	Huey R., AutoDock, Release 4.2.6, The Scripps Research Institute, La Jolla, 2014
16	http: //autodock.scripps.edu/
17	http: //mgtools.scripps.edu/
18	DeLano W., PyMOL Release 2.2.0, CA: DeLano Scientific LLC., Palo Alto, 2006
19	https: //pymol.org/2/2
20	https: //www.rcsb.org/structure/1AO6
21	https: //pubchem.ncbi.nlm.nih.gov/
22	Chen S. H., Cui X. Q., Yang F., Ni Y. N., Yang X. R., Chem. J. Chinese Universities, 2003, 24(10), 1770―1774(陈受慧, 崔小强, 杨帆, 倪永年, 杨秀荣. 高等学校化学学报, 2003, 24(10), 1770―1774)
23	Rodriguez E. A., Li X., Lehmler H. J., Robertson L. W., Duffel M. W., Environ. Sci. Technol., 2016, 50, 5320―5327
24	Xu S. W., Lin D. Q., Yao S. J., Acta Phys. Chim. Sin., 2016, 32(7), 1819―1828(徐诗文, 林东强, 姚善泾. 物理化学学报, 2016, 32(7), 1819―1828)
25	Dong L., Yi Z. S., Wu Z. W., Wang H. Y., Zhang A. Q., Acta Sci. Circumst., 2016, 36, 332―339(董露, 易忠胜, 伍智蔚, 王海洋, 张爱茜. 环境科学学报, 2016, 36, 332―339)

Compound	10^-3k_a/(L·mol^-1·s^-1)	10²k_d/s^-1	10⁵K_D/(mol·L^-1)
BDE28	1.94	6.86	3.54
BDE47	1.86	3.42	1.84
BDE99	5.77	3.92	0.68
BDE100	1.14	1.76	1.54
BDE153	7.66	1.45	0.19
BDE154	5.60	2.39	0.43
BDE183	5.34	0.87	0.16
BDE209	0.30	0.98	3.24

Compound	10^-3k_a/(L·mol^-1·s^-1)	10²k_d/s^-1	10⁵K_D/(mol·L^-1)
BDE28	1.94	6.86	3.54
BDE47	1.86	3.42	1.84
BDE99	5.77	3.92	0.68
BDE100	1.14	1.76	1.54
BDE153	7.66	1.45	0.19
BDE154	5.60	2.39	0.43
BDE183	5.34	0.87	0.16
BDE209	0.30	0.98	3.24

Compound	10⁵K_D/(mol·L^-1)	R_max/RU	Chi²
BDE28	3.93	113.30	3.06
BDE47	2.13	210.98	6.53
BDE99	0.67	108.00	13.09
BDE100	1.94	243.01	69.50
BDE153	0.21	53.58	3.88
BDE154	0.44	62.35	22.70
BDE183	0.18	33.40	10.10
BDE209	2.70	37.10	15.69

Compound	10⁵K_D/(mol·L^-1)	R_max/RU	Chi²
BDE28	3.93	113.30	3.06
BDE47	2.13	210.98	6.53
BDE99	0.67	108.00	13.09
BDE100	1.94	243.01	69.50
BDE153	0.21	53.58	3.88
BDE154	0.44	62.35	22.70
BDE183	0.18	33.40	10.10
BDE209	2.70	37.10	15.69

Compound	Theoretical			Experimental
Compound	Electrostatic binding energy/(kJ·mol^-1)	VDW and H binding energy/(kJ·mol^-1)	ΔG/(kJ·mol^-1)	ΔG/(kJ·mol^-1)
BDE28	-0.54	-33.23	-31.31	-25.40
BDE47	-0.38	-34.07	-31.98	-27.03
BDE99	-0.21	-35.49	-33.23	-29.49
BDE100	0.04	-34.69	-32.14	-27.46
BDE153	0.04	-38.08	-35.53	-32.66
BDE154	0.13	-36.99	-34.40	-30.65
BDE183	-0.04	-42.85	-40.38	-33.05
BDE209	-0.04	-33.94	-31.48	-25.62