{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0000787052,0.0001196285,0.0001082684,0.00001799775,0.00004786262,0.000005911006,0.0001118209,0.0001493567,0.00002283281],"category_scores_gemma":[0.0001580884,0.00009692094,0.00007679703,0.00005669925,0.0001347651,0.000007496851,0.00006528243,0.00003890301,0.000008194167],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00005169222,"about_ca_system_score_gemma":0.0001881596,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000004553779,"about_ca_topic_score_gemma":0.000002359594,"domain_scores_codex":[0.9992893,0.00002382338,0.0001613569,0.0002125642,0.000160475,0.000152533],"domain_scores_gemma":[0.9995028,0.00002353597,0.0001320157,0.0001945045,0.0001008142,0.00004636227],"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":[0.00005627101,0.00005209363,0.001720934,0.00007724522,0.00004145027,5.059759e-7,0.00002375965,0.00002622547,0.9961692,0.0001694956,0.0003369273,0.001325858],"study_design_scores_gemma":[0.0006652317,0.00007184999,0.02133139,0.00004464284,0.00001099765,0.00002223692,0.00001874917,0.0002111341,0.9767091,0.0002343233,0.0005326823,0.0001476183],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9681801,0.0002044746,0.02929006,0.00008774103,0.00007351986,0.0001146498,0.00005367294,0.00001702509,0.001978806],"genre_scores_gemma":[0.9973378,0.00002030573,0.001567478,0.00002122802,0.0001151247,0.00002216259,0.00007128823,0.00001031525,0.0008342821],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02915777,"threshold_uncertainty_score":0.3952321,"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."}}