ObjectiveOpioid　receptor,a　kind　of　G　protein-coupled　receptors(GPCRs),mainly　mediates　ananalgesic　responseviaallosterically　transducing　the　signal　of　endogenous　ligand　binding　in　the　extracellulardomain　to　couple　to　effector　proteins　in　the　intracellular　domain.delta　opioid　receptor(DOP)is　associated　withemotional　control　besides　pain　control,which　makes　it　an　attractive　therapeutic　target.However,its　allostericmechanism　and　key　residues　responsible　for　structural　stability　and　signal　transmission　are　not　completely　clear.This　paper　aims　to　analyze　the　structural　dynamics　and　allosteric　effects　of　DOP.MethodsFirstly,therelationships　between　DOP　structure　dynamics　and　function　were　explored　by　means　of　residue　fluctuations　inslow　motion　mode　and　fast　motion　mode　from　the　anisotropic　network　model(ANM).Then,perturbationresponse　scanning(PRS)was　used　to　identify　key　residues　related　to　allosteric　communication　in　DOP.ResultsThe　DOP　segments　and　functional　sodium-binding　sites　can　be　well　identified　by　the　slowest　motionmodes,and　the　key　residues　that　play　a　crucial　role　in　protein　structural　stability　can　be　identified　by　the　fastestmotion　modes.Correlation　analysis　of　residue　motions　reveals　positive　correlations　between　extracellular/intracellular　transmembrane　helices　and　loops,which　promote　the　DOP　structural　stability　and　the　binding　ofDOP　with　ligands.Key　residues　with　high　sensitivity　and　high　effectiveness　in　PRS　analysis　play　an　importantrole　in　the　allosteric　communication　of　DOP.ConclusionThis　work　sheds　light　on　the　allosteric　communicationmechanism　of　delta　opioid　receptor　and　provides　valuable　information　for　drug　design