{"id":"W4400686815","doi":"10.1021/acsptsci.4c00330","title":"Exploring an Intracellular Allosteric Site of CC-Chemokine Receptor 4 from 3D Models, Probe Simulations, and Mutagenesis","year":2024,"lang":"en","type":"article","venue":"ACS Pharmacology & Translational Science","topic":"Receptor Mechanisms and Signaling","field":"Biochemistry, Genetics and Molecular Biology","cited_by":4,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"HORIZON EUROPE Marie Sklodowska-Curie Actions; University of Glasgow; Biotechnology and Biological Sciences Research Council; European Commission; Queen's University; Queen's University Belfast","keywords":"Allosteric regulation; In silico; Homology modeling; Molecular dynamics; Computational biology; Chemistry; Mutagenesis; CC chemokine receptors; G protein-coupled receptor; Chemokine receptor; Binding site; Biophysics; Biology; Receptor; Biochemistry; Chemokine; Mutant; Gene; Computational chemistry","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0002108835,0.0006504916,0.0005709102,0.0002215965,0.0003657765,0.0003631873,0.0007609853,0.0005455412,0.002226804],"category_scores_gemma":[0.0003320438,0.0002747115,0.0004246827,0.0002341488,0.0002211828,0.0003372829,0.0003183156,0.0005682376,0.0002960065],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0006968085,"about_ca_system_score_gemma":0.0008662265,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.003704313,"about_ca_topic_score_gemma":0.004578148,"domain_scores_codex":[0.9999269,0.00001185722,0.000002906407,0.00001479771,0.00002728334,0.00001629889],"domain_scores_gemma":[0.9999111,0.00004907436,0.000009216492,0.000008091546,0.00001201109,0.00001055995],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"simulation_or_modeling","study_design_gemma":"simulation_or_modeling","study_design_scores_codex":[0.0003349777,0.0001784321,0.001975469,0.0002405526,0.00008566786,0.0005624741,0.0001442001,0.7881234,0.1917965,0.006092114,0.0008891051,0.009577099],"study_design_scores_gemma":[0.00004262563,0.0001109523,0.0004580262,0.000005396301,0.00001836158,0.00002970668,0.00002691012,0.975106,0.02272408,0.0007618505,0.0007034907,0.00001260652],"study_design_candidate":"simulation_or_modeling","study_design_consensus":"simulation_or_modeling","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.938188,0.0002646112,0.05454443,0.0002077435,0.0000216171,0.00008772687,0.001030925,0.0008000358,0.004855046],"genre_scores_gemma":[0.9555462,0.0004539592,0.04151456,0.0000637292,0.000007828391,0.0002801096,0.001088812,0.0001867125,0.0008580961],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003704313,"threshold_uncertainty_score":0.007449389,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.0557253892349794,"score_gpt":0.2920995912128945,"score_spread":0.2363742019779151,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}