{"id":"W4415363113","doi":"10.21203/rs.3.rs-7575211/v1","title":"Structural Insights into the Binding Modes of SHP2 Allosteric Inhibitors","year":2025,"lang":"","type":"preprint","venue":"Research Square","topic":"Protein Tyrosine Phosphatases","field":"Biochemistry, Genetics and Molecular Biology","cited_by":0,"is_retracted":false,"has_abstract":false,"ca_institutions":"University of Alberta","funders":"","keywords":"Allosteric regulation; Allosteric enzyme; Ligand (biochemistry); Plasma protein binding; Protonation; Binding pocket; Binding site; Protein tyrosine phosphatase","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":[0.0002929773,0.0009026091,0.0006192934,0.0002280796,0.0004080293,0.0008466903,0.0007895898,0.0005482281,0.005139268],"category_scores_gemma":[0.0003383731,0.0004324511,0.0003041328,0.0002861998,0.0003654665,0.0007418642,0.0003941995,0.001694242,0.0008620215],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0006360469,"about_ca_system_score_gemma":0.0004788091,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001360272,"about_ca_topic_score_gemma":0.001431576,"domain_scores_codex":[0.9998733,0.00001792571,0.000005642566,0.00002192476,0.00005054913,0.00003066021],"domain_scores_gemma":[0.999928,0.00003031935,0.00001210556,0.000006073489,0.0000082963,0.00001505253],"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":[0.002006118,0.0004220667,0.00147863,0.00101749,0.0001424408,0.001617774,0.000353536,0.04852933,0.8417357,0.05688569,0.008939178,0.03687193],"study_design_scores_gemma":[0.0004335323,0.0004149635,0.003541785,0.00009159004,0.0002032115,0.00123611,0.0004392429,0.1975242,0.7285467,0.02670452,0.04076062,0.000103529],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9047015,0.01651186,0.04065289,0.004431059,0.0003249877,0.00007930848,0.001425573,0.001113887,0.03075889],"genre_scores_gemma":[0.9822552,0.006261631,0.005714439,0.0003225485,0.00005525448,0.00003305213,0.0007279218,0.00005584516,0.004574005],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.005139268,"threshold_uncertainty_score":0.01719254,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.03624317702995697,"score_gpt":0.3654521441538124,"score_spread":0.3292089671238554,"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."}}