Allostery is a widespread mechanism that allows for precise protein tuning. Its underlying mechanisms are elusive, particularly when there are multiple allosteric sites at the protein. This concerns also G-protein-coupled receptors (GPCRs), which are targets for vast part of currently used drugs. To address this issue, we performed molecular dynamics simulations of a GPCR - human μ opioid receptor (MOR) in native-like environment, with full agonist (R)-methadone, Na(+) ions and a positive modulator (PAM) BMS986122 in various configurations. We found that MOR's 7th transmembrane helix (TM VII) is central for allosteric signal transmission, and modulators affect its bending and rotation. The PAM stabilizes favorable agonist interaction, while Na(+) tends to disrupt agonist binding. We identified two residues involved in allosteric signal transmission - Trp 7.35 at the top and Tyr 7.53 at the bottom of TM VII.