{"id":"W4407991635","doi":"10.1101/2025.02.21.639315","title":"Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release","year":2025,"lang":"en","type":"preprint","venue":"bioRxiv (Cold Spring Harbor Laboratory)","topic":"Enzyme Structure and Function","field":"Materials Science","cited_by":0,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Ottawa","funders":"","keywords":"Substrate (aquarium); Catalysis; Chemistry; Enzyme; Product (mathematics); Substrate specificity; Biochemistry; Combinatorial chemistry; Stereochemistry; Biology; Mathematics","routes":{"ca_aff":true,"ca_fund":false,"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":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0007036642,0.0004569814,0.0005034124,0.0003261541,0.0002633219,0.0003171324,0.0003074431,0.0002555359,0.00003267603],"category_scores_gemma":[0.0006026361,0.0004884354,0.00007263682,0.0006575686,0.0001712672,0.0003216567,0.0002281421,0.0004726248,0.00002055955],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002124317,"about_ca_system_score_gemma":0.000444052,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003499184,"about_ca_topic_score_gemma":0.00004156199,"domain_scores_codex":[0.9971542,0.0002165394,0.0006147365,0.001249489,0.000283735,0.0004813301],"domain_scores_gemma":[0.9984168,0.0001698008,0.0003521152,0.0006961622,0.0002189582,0.0001460961],"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":[0.00002655211,0.00004149888,0.002214732,0.0004152351,0.00002713202,0.00001422274,0.00007475873,0.0001537256,0.9967324,0.0001269585,0.0001673471,0.000005419898],"study_design_scores_gemma":[0.0002294907,0.00002205252,0.006805569,0.0003012025,0.00008498993,1.374578e-8,0.00002785197,0.000133914,0.9917565,0.000005510836,0.0001363352,0.0004965562],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9930846,0.002523558,0.002100631,0.0000845439,0.0007193913,0.0005615044,0.0006996298,0.0002163649,0.000009779103],"genre_scores_gemma":[0.9943054,0.0001043488,0.00512547,0.00003109259,0.0001370642,0.0002153265,0.000004682169,0.00003487909,0.00004173339],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.004975904,"threshold_uncertainty_score":0.9997568,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.008692289787057404,"score_gpt":0.2243558392631395,"score_spread":0.2156635494760821,"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."}}