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Computational investigation of the molecular conformation-dependent binding mode of (E)-β-farnesene analogs with a heterocycle to aphid odorant-binding proteins

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Abstract

Odorant-binding proteins (OBPs) play an important role as ligand-transfer filters in olfactory recognition in insects. (E)-β-farnesene (EBF) is the main component of the aphid alarm pheromone and could keep aphids away from crops to prevent damage. Computational insight into the molecular binding mode of EBF analogs containing a heterocycle based on the structure of Megoura viciae OBP 3 (MvicOBP3) was obtained by molecular docking and molecular dynamics simulations. The results showed that high affinity EBF analogs substituted with an aromatic ring present a unique binding conformation in the surface cavity of MvicOBP3. A long EBF chain was located inside the cavity and was surrounded by many hydrophobic residues, while the substituted aromatic ring was exposed to the outside due to limitations from the formation of multiple hydrogen bonds. However, the low activity EBF analogs displayed an exactly inverted binding pose, with EBF loaded on the external side of the protein cavity. The affinity of the recently synthesized EBF analogs containing a triazine ring was evaluated in silico based on the binding modes described above and in vitro through fluorescence competitive binding assay reported later. Compound N1 not only showed a similar binding conformation to that of the high affinity analogs but was also found to have a much higher docking score and binding affinity than the other analogs. In addition, the docking score results correlated well with the predicted logP values for these EBF analogs, suggesting highly hydrophobic interactions between the protein and ligand. These studies provide an in silico screening model for the binding affinity of EBF analogs in order to guide their rational design based on aphid OBPs.

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Acknowledgments

This study was supported by the National Key Research and Development Plan (2017YFD0200504) and the National Natural Science Foundation of China (NSFC) (No. 31772207, 31371946, 31272075) and State Key Laboratory Open Fund for Biology of Plant Diseases and Insect Pests (SKLOF201709).

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

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

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  1. Shaoqing Du
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  2. Zhaokai Yang
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  3. Yaoguo Qin
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  4. Shanshan Wang
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  5. Hongxia Duan
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Contributions

S.Q. Du, Z.K. Yang, S.S. Wang and H.X. Duan conceived and designed the experiments. Y.G. Qin synthesized the EBF compounds containing a triazine ring; S.Q. Du 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.

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Correspondence to Hongxia Duan.

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Du, S., Yang, Z., Qin, Y. et al. Computational investigation of the molecular conformation-dependent binding mode of (E)-β-farnesene analogs with a heterocycle to aphid odorant-binding proteins. J Mol Model 24, 70 (2018). https://doi.org/10.1007/s00894-018-3612-0

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