Programme

P.40 -- Posters, VCTP-51

Date: Tuesday, 4 August 2026

Time: 09:30 - 10:30

Investigating the binding of agonists to the stability of µ-opioid receptor

Hien T. T. Lai, Phung Anh Tue, and Toan T. Nguyen*

VNU Key Laboratory "Multiscale Simulation of Complex Systems" VNU University of Science, Vietnam National University 334 Nguyen Trai Street, Thanh Xuan, Hanoi, VIETNAM

Opioid agonists expressing analgesia are usually followed by adverse reactions such as heart failure, respiratory depression, constipation, etc. Agonist binding to µ-opioid receptors (µOR) can activate two intracellular signaling pathways: (i) the G protein signal is responsible for alleviating pain; (ii) β-arrestin results in unwanted side effects. Here, we utilize recent advances in computational power and molecular dynamics (MD) simulations to analyze and evaluate the influences of unbiased (Morphine – M6G) and biased (TRV130) compounds of the G protein signal, on the structural stability and functions of the µOR receptor. We have identified that M6G with hydroxyl groups, forms hydrogen bonds and electrostatic interactions with key residues in the catalytic site of the µOR receptor, whereas TRV130 prefers binding by hydrophobic and van der Waals interaction types. The binding to M6G leads to the higher flexibility of the µOR’s TM VII, which is known to activate the β-arrestin signal, while this TM VII is more stable in the TRV130-µOR complex. Additionally, the allosteric pockets of the Sodium (Na+) ion are different in these µOR complexes. Taken together, these studies may provide new avenues for the design of biased opioids with appropriate efficacy.

Presenter: Lai T. T. Hien