{"id":"W4378718044","doi":"10.7554/elife.83477","title":"Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics","year":2023,"lang":"en","type":"article","venue":"eLife","topic":"Receptor Mechanisms and Signaling","field":"Biochemistry, Genetics and Molecular Biology","cited_by":34,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"Office of Advanced Cyberinfrastructure; National Institutes of Health; Japan Science and Technology Agency; National Health and Medical Research Council; Monash University; Precursory Research for Embryonic Science and Technology; National Energy Research Scientific Computing Center; Takeda Science Foundation; Australian Research Council; Wellcome Trust; National Institute of General Medical Sciences; Medical Research Council; Wellcome","keywords":"Allosteric regulation; Drug discovery; Allosteric modulator; G protein-coupled receptor; Cooperativity; Agonist; Biophysics; Muscarinic acetylcholine receptor; Chemistry; Allosteric enzyme; Receptor; Neuroscience; Computational biology; Pharmacology; Biology; Biochemistry","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001902632,0.0001995308,0.0002388408,0.00009525101,0.0002251968,0.0002580246,0.0003831436,0.000354995,0.001000774],"category_scores_gemma":[0.0003422145,0.0002052025,0.0002629007,0.00007002078,0.000537472,0.0004965516,0.00022088,0.0007485628,0.0001192399],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0004646455,"about_ca_system_score_gemma":0.0002429049,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0009275568,"about_ca_topic_score_gemma":0.001079268,"domain_scores_codex":[0.9999266,0.00001226117,0.000004832938,0.00001470798,0.0000265504,0.00001499967],"domain_scores_gemma":[0.9999058,0.00002693317,0.00002829272,0.00001560681,0.00001301972,0.00001033838],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.0002072384,0.00007567307,0.001997039,0.0001414414,0.00003372942,0.000174302,0.0001119731,0.01381989,0.9724849,0.00531849,0.0003217714,0.005313444],"study_design_scores_gemma":[0.0001277348,0.0008179251,0.03595708,0.00003828195,0.00008515881,0.0005307086,0.0002038521,0.3823728,0.5679465,0.007292528,0.004562653,0.00006472631],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9840456,0.00106364,0.01065727,0.0004355693,0.00001707365,0.00003350167,0.0001639201,0.0001344218,0.003448957],"genre_scores_gemma":[0.9957771,0.0005994214,0.003063545,0.00007986761,0.000004974266,0.00003097281,0.0001018641,0.00001117131,0.0003311023],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001000774,"threshold_uncertainty_score":0.003371298,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01319784367478989,"score_gpt":0.2657993716343126,"score_spread":0.2526015279595227,"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."}}