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bioRxiv · 10.1101/2021.12.02.470941

Differential recognition of opioid analgesics by μ opioid receptors: Predicted interaction patterns correlate with ligand-specific voltage sensitivity

Kirchhofer, S. B.·Lim, V. J. Y.·Julia, R. G.·Kolb, P.·Buenemann, M.
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Abstract

The {micro} opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties in receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and resulting effects is important. Here, we calculated the respective binding modes for several opioids and analyzed fingerprints of ligand-receptor interactions. We further corroborated the binding modes experimentally by cellular assays. As ligand-induced modulation of activity due to changes in membrane potential was displayed by MOR, we further analyzed the effects of voltage sensitivity of this receptor. With a combined in silico and in vitro approach, we defined discriminating interaction patterns for the ligand-specific voltage sensitivity. With this, we present new insights for interactions likely in ligand recognition and their specific effects on activation of the MOR.

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Kirchhofer, S. B., Lim, V. J. Y., Julia, R. G., Kolb, P., Buenemann, M.. 2021-12-03. Differential recognition of opioid analgesics by μ opioid receptors: Predicted interaction patterns correlate with ligand-specific voltage sensitivity. https://doi.org/10.1101/2021.12.02.470941

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