{"id":"W2966719369","doi":"10.1002/chem.201901664","title":"Targeting a Large Active Site: Structure‐Based Design of Nanomolar Inhibitors of <i>Trypanosoma brucei</i> Trypanothione Reductase","year":2019,"lang":"en","type":"article","venue":"Chemistry - A European Journal","topic":"Research on Leishmaniasis Studies","field":"Medicine","cited_by":19,"is_retracted":false,"has_abstract":true,"ca_institutions":"Canada Research Chairs; University Health Network; University of Toronto; Ontario Institute for Cancer Research; University of New Brunswick","funders":"Natural Sciences and Engineering Research Council of Canada; University of Toronto; Deutsche Forschungsgemeinschaft","keywords":"Trypanosoma brucei; Active site; IC50; Biochemistry; HEPES; Binding site; Enzyme; Chemistry; In vivo; In vitro; Glutathione; Biology; Stereochemistry","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":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0005449946,0.0003291045,0.0007155424,0.0001276196,0.0001563084,0.00003507314,0.0003268477,0.00008574136,0.0008651813],"category_scores_gemma":[0.001174067,0.0002791092,0.0002616106,0.0003743007,0.0002226792,0.0001561176,0.0001685982,0.001028592,0.00002736453],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001428653,"about_ca_system_score_gemma":0.0004508114,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000002156481,"about_ca_topic_score_gemma":6.089325e-8,"domain_scores_codex":[0.9967542,0.0004685809,0.0009212145,0.0003967031,0.0008931032,0.0005661959],"domain_scores_gemma":[0.9974435,0.0001682207,0.0008378519,0.0004864273,0.0007281259,0.0003358489],"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":[0.001070161,0.0002812652,0.001779873,0.0006167475,0.0002330059,0.0004547419,0.0006949044,0.0001686808,0.9906685,9.967238e-7,0.003500933,0.0005302185],"study_design_scores_gemma":[0.005134852,0.0004935042,0.003286865,0.0008298683,0.0001189736,0.000563672,0.0009334148,0.0007091956,0.9861792,0.000009851365,0.001482045,0.0002586],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.99623,0.0007456572,0.0006660106,0.000276414,0.0001360162,0.0003657337,0.0001225471,0.00003132053,0.001426268],"genre_scores_gemma":[0.9949282,0.00009171394,0.003927402,0.00009478255,0.0004517606,0.000001803454,0.0000396,0.00008669306,0.0003780822],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.004489313,"threshold_uncertainty_score":0.9999661,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01541240844596871,"score_gpt":0.2547431659412177,"score_spread":0.239330757495249,"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."}}