{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.001615423,0.0001977552,0.0005357834,0.0001103979,0.0005971886,0.00005904612,0.0009152978,0.00006447325,0.00006057429],"category_scores_gemma":[0.001365015,0.0001064046,0.0001235431,0.0002068174,0.001103407,0.0001336347,0.0008519263,0.0004368524,0.000009439433],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00007264315,"about_ca_system_score_gemma":0.00007608723,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001922722,"about_ca_topic_score_gemma":0.000032244,"domain_scores_codex":[0.9979637,0.0004512412,0.0003974214,0.0003618149,0.0004335744,0.0003922011],"domain_scores_gemma":[0.9973282,0.001222422,0.0003894474,0.0007689243,0.0001480568,0.0001429726],"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":[0.0005959439,0.00003201611,0.01207358,0.0001297648,0.0001718243,0.00001798522,0.0006335914,0.0001666178,0.9850659,0.000008766032,0.0001804937,0.0009235141],"study_design_scores_gemma":[0.00247332,0.0006343392,0.02551358,0.0005892692,0.0004302512,0.00002829312,0.0001765472,0.00147309,0.9678734,0.00001531703,0.0006561376,0.0001364766],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9939653,0.001440155,0.0003693059,0.002427051,0.0003443542,0.001291758,0.00002392848,0.00001704046,0.0001211147],"genre_scores_gemma":[0.9991353,0.00008047089,0.000240592,0.0002009861,0.0001139822,0.00005702144,0.00000322271,0.00003039697,0.0001380746],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01719252,"threshold_uncertainty_score":0.4593152,"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."}}