{"id":"W2952030874","doi":"10.1021/acsomega.9b00640","title":"Structure-Based Design of Dimeric Bisbenzimidazole Inhibitors to an Emergent Trimethoprim-Resistant Type II Dihydrofolate Reductase Guides the Design of Monomeric Analogues","year":2019,"lang":"en","type":"article","venue":"ACS Omega","topic":"Biochemical and Molecular Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":10,"is_retracted":false,"has_abstract":true,"ca_institutions":"Université de Sherbrooke; Institute for Research in Immunology and Cancer; Centre in Green Chemistry and Catalysis; McGill University; Université de Montréal; PROTEO","funders":"Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research; Hydro-Québec; Canada Foundation for Innovation; McGill University; Fonds Québécois de la Recherche sur la Nature et les Technologies; Canadian Light Source","keywords":"Dihydrofolate reductase; Trimethoprim; Chemistry; Combinatorial chemistry; Stereochemistry; Monomer; Biochemistry; Enzyme; Antibiotics; Organic chemistry","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":[0.0002348802,0.0004728292,0.0004275455,0.0001817914,0.0002315674,0.0005377298,0.0007966612,0.0004431986,0.002085557],"category_scores_gemma":[0.0002366037,0.0002808416,0.0002799776,0.0001856735,0.000240597,0.0002180586,0.0002022116,0.001101249,0.001000647],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00103371,"about_ca_system_score_gemma":0.0006498945,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001527507,"about_ca_topic_score_gemma":0.005774383,"domain_scores_codex":[0.9998858,0.00002072907,0.00000913291,0.00002410271,0.00003487467,0.00002526716],"domain_scores_gemma":[0.9999304,0.000005543707,0.00001856719,0.000006274322,0.00001997639,0.00001911766],"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":[0.0003484055,0.00034888,0.0004186,0.0001798449,0.00003752584,0.000219868,0.00007754748,0.007893844,0.9676949,0.003683745,0.001212368,0.01788442],"study_design_scores_gemma":[0.0006182586,0.002134918,0.001047461,0.0000458231,0.0001206123,0.0005602723,0.0001068798,0.02700734,0.9323608,0.0008575456,0.03508639,0.00005358147],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.8801568,0.006555506,0.09063039,0.001330889,0.0003238899,0.0008616258,0.0009218893,0.0009217644,0.01829729],"genre_scores_gemma":[0.9527324,0.003060763,0.03676473,0.0003015331,0.00002190975,0.0001576597,0.001010272,0.00006595507,0.005884803],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002085557,"threshold_uncertainty_score":0.007500112,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02718697785575197,"score_gpt":0.2892980911679296,"score_spread":0.2621111133121777,"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."}}