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There is a resurgence of interest in G protein-coupled receptor (GPCR) structure-guided drug design due to the rapid increase in high-resolution structures of these biologically important proteins. The μ opioid receptor (MOPr) is an important GPCR, both therapeutically for analgesia and in drug abuse. There are opportunities to develop new opioids which exhibit distinct efficacies for different signalling pathways, a phenomenon known as agonist bias. This could represent a strategy to fine-tune MOPr activation, directing signalling towards analgesia whilst avoiding adverse effects. However, the mechanisms underlying ligand efficacy and agonist bias at the MOPr remain poorly understood. With this in mind, we employed molecular dynamics (MD) simulations of ligand-MOPr complexes to identify potential structural signatures of MOPr activation and biased agonism. Small molecules and peptides were selected for their differing efficacies and bias profiles, docked to the inactive MOPr and 1 μs MD simulations performed. On a residue-level, these MD simulations predicted that opioids adopt distinct binding poses and therefore interact with different subsets of residues. Specifically, high efficacy agonists induced conformational changes in the W2936.48 microswitch. Mutagenesis of this residue resulted in a receptor which did not respond to agonists, indicating that W2936.48 is essential for MOPr activation. Comparison of the arrestin-biased peptide, endomorphin-2, with the novel G protein-biased peptide, bilorphin, revealed that interaction with the MOPr extracellular loops may indicate bias towards arrestin recruitment. On the level of the transmembrane domains, the MOPr adopted distinct conformations which differentiated high efficacy ligands from those of lower efficacy, as well as agonists of opposing bias. Conformational changes in the MOPr helices were prevented by an allosteric sodium ion or the W2936.48A mutation. This work builds on evidence that GPCRs occupy multiple conformations dependent on the bound ligand. Moreover, this thesis identifies key residues which may be important in conferring ligand efficacy and agonist bias at the MOPr.