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Computer-aided rational design of novel EBF analogues with an aromatic ring

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Abstract

Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π–π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1–D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure.

The design strategy of new EBF analogues based on the OBP7 structure

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Acknowledgments

We thank Dr. Pelosi for fruitful discussions and writing assistance. This work was supported by the National Scientific and Technology Supporting Program of China (2011BAE06B05-5) and the National Natural Science Foundation of China (21132003, 31371946).

Author contributions

S.S. Wang, S.Q. Du, and H.X. Duan conceived and designed the experiments. Y.F. Sun, Y.G. Qin, and X.L. Yang prepared the EBF analogues. S.S. Wang, Y.F. Sun, and H.X. Duan analyzed the data. S.S. Wang and H.X. Duan wrote the first draft of the manuscript. H.X. Duan and X.L. Yang made critical revisions and approved the final manuscript. All the authors reviewed and approved the final manuscript. The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China

    Shanshan Wang, Shaoqing Du, Yaoguo Qin, Hongxia Duan & Xinling Yang

  2. Laboratory of Agro-products Quality Safety Risk Assessment, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

    Yufeng Sun

Authors
  1. Shanshan Wang
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  2. Yufeng Sun
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  3. Shaoqing Du
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  4. Yaoguo Qin
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  5. Hongxia Duan
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  6. Xinling Yang
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Corresponding authors

Correspondence to Hongxia Duan or Xinling Yang.

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Wang, S., Sun, Y., Du, S. et al. Computer-aided rational design of novel EBF analogues with an aromatic ring. J Mol Model 22, 144 (2016). https://doi.org/10.1007/s00894-016-3011-3

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  • DOI: https://doi.org/10.1007/s00894-016-3011-3

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