{"id":"W2618831618","doi":"10.1124/mol.117.108373","title":"Direct Binding of the Corrector VX-809 to Human CFTR NBD1: Evidence of an Allosteric Coupling between the Binding Site and the NBD1:CL4 Interface","year":2017,"lang":"en","type":"article","venue":"Molecular Pharmacology","topic":"Cystic Fibrosis Research Advances","field":"Medicine","cited_by":93,"is_retracted":false,"has_abstract":true,"ca_institutions":"Hospital for Sick Children; University of Toronto","funders":"Cystic Fibrosis Canada; Vertex Pharmaceuticals; Cystic Fibrosis Foundation Therapeutics","keywords":"Allosteric regulation; Chemistry; Potentiator; Cyclic nucleotide-binding domain; Binding site; Cystic fibrosis transmembrane conductance regulator; Transmembrane domain; Stereochemistry; Biophysics; Crystallography; Nucleotide; Biochemistry; Membrane; Biology","routes":{"ca_aff":true,"ca_fund":true,"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":[0.0001112805,0.0002034045,0.0002844355,0.00005680836,0.0001281885,0.0001506796,0.0002812524,0.0003868059,0.001855095],"category_scores_gemma":[0.0002352508,0.0001442937,0.0001718646,0.00006266304,0.0002481314,0.0001114797,0.0002089636,0.0004922384,0.0003493878],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002913573,"about_ca_system_score_gemma":0.0001746995,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001153305,"about_ca_topic_score_gemma":0.00155056,"domain_scores_codex":[0.9998391,0.00002141878,0.00001067796,0.00003806784,0.00005860543,0.00003204322],"domain_scores_gemma":[0.9999156,0.00002306867,0.00002759343,0.000009154321,0.000008804834,0.00001584063],"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":[0.0001112327,0.00002190708,0.0002825597,0.00003959848,0.00000604539,0.00003204276,0.00001126008,0.0001112305,0.9986581,0.0000395567,0.00003924969,0.0006471782],"study_design_scores_gemma":[0.00002238855,0.000225039,0.003336356,0.000003659344,0.000008674441,0.0001459029,0.00001805423,0.0006376604,0.9949203,0.00001797597,0.000660417,0.0000034579],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9961691,0.0008306215,0.001467227,0.0001175943,0.00001926343,0.00001805146,0.0001346202,0.00002894213,0.001214518],"genre_scores_gemma":[0.9964197,0.0004656675,0.001398785,0.000136464,0.000007687542,0.00002296488,0.0002152884,0.000008717691,0.001324777],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001855095,"threshold_uncertainty_score":0.006205916,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.04436644329969548,"score_gpt":0.4146032095100438,"score_spread":0.3702367662103483,"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."}}