Mechanism of enhanced sensitivity of mutated β‐adrenergic‐like octopamine receptor to amitraz in honeybee <i>Apis mellifera</i>: An insight from <scp>MD</scp> simulations
Bibliographic record
Abstract
Abstract BACKGROUND Amitraz is one of the critical acaricides/insecticides for effective control of pest infestation of Varroa destructor mite, a devastating parasite of Apis mellifera , because of its low toxicity to honeybees. Previous assays verified that a typical G protein‐coupled receptor, β‐adrenergic‐like octopamine receptor (Octβ2R), is the unique target of amitraz, but the honeybee Octβ2R resists to amitraz. However, the underlying molecular mechanism of the enhanced sensitivity or toxicity of amitraz to mutated honeybee Octβ2R E208V/I335T/I350V is not fully understood. Here, molecular dynamics simulations are employed to explore the implied mechanism of the enhanced sensitivity to amitraz in mutant honeybee Octβ2R. RESULTS We found that amitraz binding stabilized the structure of Octβ2R, particularly the intracellular loop 3 associated with the Octβ2R signaling. Then, it was further demonstrated that both mutations and ligand binding resulted in a more rigid and compact amitraz binding site, as well as the outward movement of the transmembrane helix 6, which was a prerequisite for G protein coupling and activation. Moreover, mutations were found to promote the binding between Octβ2R and amitraz. Finally, community analysis illuminated that mutations and amitraz strengthened the residue–residue communication within the transmembrane domain, which might facilitate the allosteric signal propagation and activation of Octβ2R. CONCLUSION Our results unveiled structural determinants of improved sensitivity in the Octβ2R‐amitraz complex and may contribute to further structure‐based drug design for safer and less toxic selective insecticides. © 2022 Society of Chemical Industry.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".