Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Fentanyl binds to the mu-opioid receptor via the lipid membrane and transmembrane helices Overdose deaths from synthetic opioids, such as fentanyl, have reached epidemic proportions in the USA and are increasing worldwide. Fentanyl is a potent opioid agonist, that is less well reversed by naloxone than morphine. Due to fentanyls high lipophilicity and elongated structure we hypothesised that its unusual pharmacology may be explained by a novel binding mode to the -opioid receptor (MOPr).

By employing coarse-grained molecular dynamics simulations and free energy calculations, we determined the routes by which fentanyl and morphine access the orthosteric pocket of MOPr.

Morphine accesses MOPr via the aqueous pathway; first binding to an extracellular vestibule, then diffusing into the orthosteric pocket. In contrast, fentanyl takes a novel route; first partitioning into the membrane, before accessing the orthosteric site by diffusing through a ligand-induced gap between the transmembrane helices.

This novel lipophilic route may explain the high potency and lower susceptibility of fentanyl to reversal by naloxone.
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The categories of this paper are: animal
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The categories of this paper are: physiology
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The categories of this paper are: biophysics
3
The categories of this paper are: evolutionary
29
The categories of this paper are: education
18
The categories of this paper are: systems
15
The categories of this paper are: developmental
0
The categories of this paper are: genetics
32
The categories of this paper are: zoology
25
The categories of this paper are: bioengineering
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The categories of this paper are: cognition
30
The categories of this paper are: scientific
1
The categories of this paper are: bioinformatics
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The categories of this paper are: cell
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The categories of this paper are: ecology
31
The categories of this paper are: paleontology