Computational studies of interactions between endocrine disrupting chemicals and androgen receptor of different vertebrate species

TY - JOUR

T1 - Computational studies of interactions between endocrine disrupting chemicals and androgen receptor of different vertebrate species

AU - Wu, Bing

AU - Ford, Timothy

AU - Gu, Ji Dong

AU - Zhang, Xu Xiang

AU - Li, Ai Min

AU - Cheng, Shu Pei

N1 - Funding Information: This research work was financially supported by National Natural Science Foundation of China (No. 50938004 ), Social Development Foundation of Jiangsu Province (No. BE2009668 ) and Shanghai Tongji Gao Tingyao Environmental Science and Technology Development Foundation.

PY - 2010/7

Y1 - 2010/7

N2 - Homology modeling and molecular docking were used to in silico analyze the interactions between six endocrine disrupting chemicals (EDCs) and 11 androgen receptors (ARs) of different vertebrate species. The MODELLER 9V7 program was employed to construct the homology models of AR ligand binding domains (LBDs) from birds, amphibians, bony fishes and cartilaginous fishes. The Surflex-Dock program was applied to calculate and analyze the binding affinities between the six EDCs and AR LBDs. The docking experiment showed that AR LBDs had high affinities with nonyl phenol (NP) and butyl benzyl phthalate (BBP), but low affinities with the 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153). The results of cluster analysis suggested that predicted binding affinities were species-specific, which was consistent with the phylogenetic analysis of AR LBDs. The difference of binding affinities could be mainly due to the different hydrogen bonds and the orientation of ligands in the binding pockets. Our results suggest that integrated methods of phylogenetic analysis, homology modeling and molecular docking might be a potential tool to predict the different interactions between contaminants and associated receptors in different trophic levels.

AB - Homology modeling and molecular docking were used to in silico analyze the interactions between six endocrine disrupting chemicals (EDCs) and 11 androgen receptors (ARs) of different vertebrate species. The MODELLER 9V7 program was employed to construct the homology models of AR ligand binding domains (LBDs) from birds, amphibians, bony fishes and cartilaginous fishes. The Surflex-Dock program was applied to calculate and analyze the binding affinities between the six EDCs and AR LBDs. The docking experiment showed that AR LBDs had high affinities with nonyl phenol (NP) and butyl benzyl phthalate (BBP), but low affinities with the 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153). The results of cluster analysis suggested that predicted binding affinities were species-specific, which was consistent with the phylogenetic analysis of AR LBDs. The difference of binding affinities could be mainly due to the different hydrogen bonds and the orientation of ligands in the binding pockets. Our results suggest that integrated methods of phylogenetic analysis, homology modeling and molecular docking might be a potential tool to predict the different interactions between contaminants and associated receptors in different trophic levels.

KW - Androgen receptor

KW - Endocrine disrupting chemicals

KW - Homology modeling

KW - Molecular docking

UR - http://www.scopus.com/inward/record.url?scp=77953812306&partnerID=8YFLogxK

U2 - 10.1016/j.chemosphere.2010.04.043

DO - 10.1016/j.chemosphere.2010.04.043

M3 - 文章

C2 - 20546840

AN - SCOPUS:77953812306

SN - 0045-6535

VL - 80

SP - 535

EP - 541

JO - Chemosphere

JF - Chemosphere

IS - 5

ER -