{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004792277,0.0002294234,0.0003026208,0.0001206105,0.00007961133,0.00001336622,0.0005298232,0.0001607314,0.00002745607],"category_scores_gemma":[0.0002087805,0.0001639749,0.0001074905,0.0005696054,0.0001464719,0.000006747186,0.0002243173,0.000128106,0.000004676728],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00001771723,"about_ca_system_score_gemma":0.0002165404,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001068248,"about_ca_topic_score_gemma":0.000002121715,"domain_scores_codex":[0.9981715,0.0003202461,0.0004147997,0.0004444773,0.0003005919,0.0003483573],"domain_scores_gemma":[0.9986016,0.00004409349,0.0001675636,0.0007911355,0.0002344168,0.0001611457],"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":[0.0009545317,0.000124849,0.0001245371,0.00003351003,0.00009678194,0.00000136982,0.00005460706,0.007472042,0.9885122,0.00001419611,0.001266497,0.001344842],"study_design_scores_gemma":[0.0004188908,0.001898574,0.0002717027,0.00001845403,0.00003716584,0.00000142094,0.00004493097,0.0004450891,0.9943779,0.00006812309,0.002208944,0.0002088404],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9913394,0.001625173,0.005957991,0.000161661,0.0001447316,0.0006963651,0.00003441796,0.000009421555,0.00003077171],"genre_scores_gemma":[0.9936205,0.0001039765,0.005750606,0.0001697741,0.00005946875,0.00001870983,0.0001173578,0.00003567361,0.0001239966],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.007026953,"threshold_uncertainty_score":0.6686704,"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."}}