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<p>This study combines NMR spectroscopy, molecular dynamics (MD) simulations, and docking approaches to investigate the structure, dynamics, and receptor interactions of the decapeptide Carmo-HrTH-II from the stick insect <i>Carausius morosus</i>. NMR data indicate a flexible peptide that adopts a β-turn between Pro⁶ and Asn⁷, a feature that is also observed in MD simulations and may contribute to receptor recognition. Docking of Carmo-HrTH-II to a Carmo-AKHR homology model suggests a stable binding mode in which Phe<sup>4</sup> and Trp⁸ occupy the binding pocket, consistent with their proposed roles in GPCR activation. Alanine- and residue-scanning analyses show general agreement between calculated binding energies and experimental EC₅₀ values, supporting the importance of Phe<sup>4</sup>, Pro⁶, Asn⁷, and Trp⁸ in receptor activation. Comparative analyses of Carmo-HrTH-I and related AKH analogues suggest that substitutions at position 10 have limited effects on binding, whereas changes at position 3 may more substantially influence affinity. In silico screening of insecticide-like compounds identified several candidates that may act as receptor antagonists by binding to the same site as Carmo-HrTH-II. These ligands are predicted to interact primarily through π–π stacking and hydrogen bonding, potentially perturbing interactions associated with receptor activation. Overall, these findings provide a structural and dynamic framework for understanding AKH receptor interactions and may inform the rational design of AKH-targeted insecticides.</p>

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Molecular modelling of the adipokinetic hormone receptor from the stick insect Carausius morosus, and its endogenous agonist

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • G. E. Jackson,
  • H. G. Marco,
  • M. A. Sani,
  • F. Separovic,
  • G. Gäde

摘要

This study combines NMR spectroscopy, molecular dynamics (MD) simulations, and docking approaches to investigate the structure, dynamics, and receptor interactions of the decapeptide Carmo-HrTH-II from the stick insect Carausius morosus. NMR data indicate a flexible peptide that adopts a β-turn between Pro⁶ and Asn⁷, a feature that is also observed in MD simulations and may contribute to receptor recognition. Docking of Carmo-HrTH-II to a Carmo-AKHR homology model suggests a stable binding mode in which Phe4 and Trp⁸ occupy the binding pocket, consistent with their proposed roles in GPCR activation. Alanine- and residue-scanning analyses show general agreement between calculated binding energies and experimental EC₅₀ values, supporting the importance of Phe4, Pro⁶, Asn⁷, and Trp⁸ in receptor activation. Comparative analyses of Carmo-HrTH-I and related AKH analogues suggest that substitutions at position 10 have limited effects on binding, whereas changes at position 3 may more substantially influence affinity. In silico screening of insecticide-like compounds identified several candidates that may act as receptor antagonists by binding to the same site as Carmo-HrTH-II. These ligands are predicted to interact primarily through π–π stacking and hydrogen bonding, potentially perturbing interactions associated with receptor activation. Overall, these findings provide a structural and dynamic framework for understanding AKH receptor interactions and may inform the rational design of AKH-targeted insecticides.