{"id":"W4414654265","doi":"10.1038/s41467-025-63802-7","title":"Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release","year":2025,"lang":"en","type":"article","venue":"Nature Communications","topic":"Biochemical and Molecular Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":16,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Ottawa","funders":"Basic Energy Sciences; Lawrence Berkeley National Laboratory; National Institute of General Medical Sciences; Biological and Environmental Research; Natural Sciences and Engineering Research Council of Canada; Alliance de recherche numérique du Canada; National Institutes of Health; U.S. Department of Health and Human Services; Government of Canada; Canada Foundation for Innovation; U.S. Department of Energy","keywords":"Substrate (aquarium); Catalysis; Active site; Mutant; Enzyme; Catalytic cycle; Product inhibition; Mutation; Molecular dynamics","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":[0.0002757215,0.0004649218,0.0003764634,0.0001619687,0.0001474118,0.0004791725,0.0003635953,0.0003645527,0.0007846645],"category_scores_gemma":[0.0004598381,0.0002344488,0.0002478264,0.0001519222,0.000387991,0.0003381931,0.0004708836,0.0007530696,0.0003553312],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002712961,"about_ca_system_score_gemma":0.0002501243,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002636322,"about_ca_topic_score_gemma":0.0006568012,"domain_scores_codex":[0.9998364,0.00002538288,0.00002059218,0.00003991802,0.00005165692,0.00002596029],"domain_scores_gemma":[0.9997752,0.00006174615,0.000070789,0.00003216809,0.00002092239,0.00003905442],"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":[0.00009784499,0.00004196418,0.00047707,0.00003875922,0.00001059384,0.00009489668,0.0000185817,0.001579999,0.9953439,0.0003879154,0.00001391795,0.001894452],"study_design_scores_gemma":[0.00002345164,0.0001809753,0.001063206,0.000004209728,0.00001618345,0.0002773085,0.00001685453,0.004654027,0.9926981,0.0001559512,0.0008995552,0.0000101569],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9835764,0.0001852425,0.01507393,0.000044828,0.00001207301,0.00002503138,0.00006473275,0.0001451599,0.000872534],"genre_scores_gemma":[0.9901661,0.0001456063,0.009079721,0.00002705982,0.000002320097,0.00000956143,0.00006100375,0.00004841504,0.0004602348],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0007846645,"threshold_uncertainty_score":0.002624989,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009594425834232463,"score_gpt":0.3178802776006666,"score_spread":0.3082858517664341,"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."}}