{"id":"W4406972424","doi":"10.1016/j.molcel.2025.01.004","title":"A PARP2 active site helix melts to permit DNA damage-induced enzymatic activation","year":2025,"lang":"en","type":"article","venue":"Molecular Cell","topic":"PARP inhibition in cancer therapy","field":"Medicine","cited_by":8,"is_retracted":false,"has_abstract":false,"ca_institutions":"Université de Montréal","funders":"National Institutes of Health; National Cancer Institute; University of Pennsylvania","keywords":"Biology; Helix (gastropod); DNA; Enzyme; DNA damage; Biophysics; Cell biology; Active site; Biochemistry; DNA Ligases; Genetics; DNA repair; Molecular biology; Ecology","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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0005351772,0.0003826655,0.0004514257,0.0002186778,0.000909659,0.001007121,0.0005155,0.001172889,0.01220585],"category_scores_gemma":[0.0008454564,0.0004100931,0.0005972474,0.0002412954,0.0004576304,0.001101306,0.0006450087,0.002026032,0.004267065],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0005341926,"about_ca_system_score_gemma":0.0003632353,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002187187,"about_ca_topic_score_gemma":0.0001869328,"domain_scores_codex":[0.9995752,0.0000535183,0.00003353093,0.0001395787,0.0001124638,0.00008574249],"domain_scores_gemma":[0.9991524,0.0001340556,0.0002254824,0.0001885369,0.00008915216,0.0002103688],"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":[0.000944156,0.0001615679,0.0006792071,0.00009232843,0.00003907639,0.0005650691,0.00007947459,0.00111552,0.9859301,0.002222924,0.001854191,0.006316445],"study_design_scores_gemma":[0.00006757389,0.0004224307,0.001649353,0.00001444049,0.00001402963,0.0007543378,0.00004824344,0.001875085,0.9814998,0.0008129114,0.01281531,0.00002633382],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9370323,0.002220374,0.03955575,0.002213266,0.001352384,0.0001397079,0.001345876,0.002042985,0.01409737],"genre_scores_gemma":[0.9871185,0.0002835004,0.005267614,0.0005021499,0.0001141553,0.0000441241,0.0009874271,0.0001547275,0.00552789],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01220585,"threshold_uncertainty_score":0.0408327,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01191224472936656,"score_gpt":0.2976405904956262,"score_spread":0.2857283457662597,"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."}}