{"id":"W2495009353","doi":"10.1021/acs.biochem.6b00561","title":"Conformational Tinkering Drives Evolution of a Promiscuous Activity through Indirect Mutational Effects","year":2016,"lang":"en","type":"article","venue":"Biochemistry","topic":"Evolution and Genetic Dynamics","field":"Biochemistry, Genetics and Molecular Biology","cited_by":54,"is_retracted":false,"has_abstract":true,"ca_institutions":"Canada's Michael Smith Genome Sciences Centre; University of British Columbia","funders":"Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research","keywords":"Paraoxon; Active site; Mutagenesis; Epistasis; Alanine scanning; Mutation; Directed evolution; Biochemistry; Biology; Site-directed mutagenesis; Genetics; Alanine; Chemistry; Enzyme; Gene; Mutant; Amino acid; Acetylcholinesterase","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":[0.0003562665,0.0003856801,0.0003186293,0.0001672033,0.0002561937,0.0004661255,0.0003589335,0.0003806099,0.001002939],"category_scores_gemma":[0.0008708444,0.0001974275,0.000274372,0.0001497986,0.0005663632,0.000380049,0.0006613166,0.0007705472,0.0001457765],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003006361,"about_ca_system_score_gemma":0.0002842555,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002879891,"about_ca_topic_score_gemma":0.0005503795,"domain_scores_codex":[0.999813,0.00003894432,0.00001589595,0.00005184587,0.00004946091,0.00003086557],"domain_scores_gemma":[0.9997293,0.00009809818,0.0000634638,0.00005049874,0.00002071326,0.00003782411],"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":[0.0001649473,0.0001197615,0.005361045,0.00006378379,0.00005484921,0.0004029211,0.00008245401,0.009653398,0.9728634,0.001888702,0.0000370653,0.009307704],"study_design_scores_gemma":[0.0001292095,0.001748992,0.03883546,0.00002756359,0.0001664996,0.002037222,0.0003029189,0.1998883,0.7483821,0.005465917,0.002931364,0.00008454405],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.994552,0.00005235804,0.004690465,0.00003110578,0.000006207021,0.000009896558,0.00001268944,0.00008048728,0.0005649453],"genre_scores_gemma":[0.9975299,0.00005951468,0.00218145,0.00002260875,0.000002054446,0.00000925876,0.00002010174,0.00002169041,0.000153369],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001002939,"threshold_uncertainty_score":0.003355145,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.004374208439234705,"score_gpt":0.2290757527016249,"score_spread":0.2247015442623902,"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."}}