Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

This article is part of the supplement: Proceedings of the Tenth Annual MCBIOS Conference

Open Access Open Badges Proceedings

Homology modeling, molecular docking, and molecular dynamics simulations elucidated α-fetoprotein binding modes

Jie Shen1, Wenqian Zhang1, Hong Fang2, Roger Perkins1, Weida Tong1 and Huixiao Hong1*

Author Affiliations

1 Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA

2 Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA

For all author emails, please log on.

BMC Bioinformatics 2013, 14(Suppl 14):S6  doi:10.1186/1471-2105-14-S14-S6

Published: 9 October 2013



An important mechanism of endocrine activity is chemicals entering target cells via transport proteins and then interacting with hormone receptors such as the estrogen receptor (ER). α-Fetoprotein (AFP) is a major transport protein in rodent serum that can bind and sequester estrogens, thus preventing entry to the target cell and where they could otherwise induce ER-mediated endocrine activity. Recently, we reported rat AFP binding affinities for a large set of structurally diverse chemicals, including 53 binders and 72 non-binders. However, the lack of three-dimensional (3D) structures of rat AFP hinders further understanding of the structural dependence for binding. Therefore, a 3D structure of rat AFP was built using homology modeling in order to elucidate rat AFP-ligand binding modes through docking analyses and molecular dynamics (MD) simulations.


Homology modeling was first applied to build a 3D structure of rat AFP. Molecular docking and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) scoring were then used to examine potential rat AFP ligand binding modes. MD simulations and free energy calculations were performed to refine models of binding modes.


A rat AFP tertiary structure was first obtained using homology modeling and MD simulations. The rat AFP-ligand binding modes of 13 structurally diverse, representative binders were calculated using molecular docking, (MM-GBSA) ranking and MD simulations. The key residues for rat AFP-ligand binding were postulated through analyzing the binding modes.


The optimized 3D rat AFP structure and associated ligand binding modes shed light on rat AFP-ligand binding interactions that, in turn, provide a means to estimate binding affinity of unknown chemicals. Our results will assist in the evaluation of the endocrine disruption potential of chemicals.